Cell Sentence Context

Table 1. Analysis of context sentence of endothelial tissue in 624 abstracts.

PMID Senteces
32227090 The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction.
32271454 The protein-protein interaction network exhibited hub targets of MXSGD, such as Heat shock protein 90, RAC-alpha serine/threonine-protein kinase, Transcription factor AP-1, Mitogen-activated protein kinase 1, Cellular tumor antigen p53, Vascular endothelial growth factor A, and Tumour necrosis factor.
32306290 Due to the hypercoagulable state, blood stasis and endothelial injury, severe patients with COVID-19 are at high risk for thrombosis.
32311448 Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis.
32314810 We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).
32328757 There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic.
32329246 Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state.
32330302 I would like to talk about the role of ACE2 in endothelial cell function. […] Besides, I would like to mention that COVID-19 patients might benefit from ACEI/ARBs concerning improving endothelial dysfunction in COVID-19.
32333487 The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared with previous CoVs.
32338224 SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6].
32338605 We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs.
32352535 This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).
32374430 The current pandemic and its pleotropic effects can be explained in part by interaction between SARS-CoV-2 spike protein S, the ACE2/L-SIGN/CD209 receptor on the type II alveolar cell of the lung, and the DC-SIGN receptor on the respiratory dendritic cell (DC) and associated endothelial cells.
32375845 Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation.
32378030 The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells.
32380958 Stress induces apoptosis in pulmonary endothelial cells from females but necrosis in cells from males.
32383264 A very interesting report, for the first time, provided direct evidence that the ongoing pandemic etiological agent, SARS-CoV-2, may be able to directly infect central nervous system (CNS) through an endothelial route.
32395910 It has been hypothesized that COVID-19 lung involvement could represent not only a viral effect but also an immune response induced by the infection, causing epithelial/endothelial lesions and coagulation disorders.
32403201 Recent articles published in Obesity (1-3) discuss the possible effects of increased proinflammatory cytokines and disturbances of lung function in people with obesity, but we believe that they overlook an important player in this scenario, which is endothelial dysfunction.
32405120 Increasing evidence points to endothelial cell dysfunction as a key pathophysiological factor in severe coronavirus disease-19 (COVID-19), manifested by platelet aggregation, microthrombi and altered vasomotor tone. […] This may be driven by direct endothelial cell entry by the virus, or indirectly by activated inflammatory cascade. […] In this article, we propose that pre-existing endothelial dysfunction of microangiopathy, more commonly evident in diabetes and BAME groups, makes an individual vulnerable to the subsequent ‘endothelitis’ of COVID-19 infection.
32405226 Artemisinins can regulate the expression of pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), promote cell cycle arrest, drive reactive oxygen species (ROS) production and induce Bak or Bax-dependent or independent apoptosis.
32408155 As an S1P analogue, fingolimod might enhance lung endothelial cell integrity.
32414626 Patients with metastatic renal cancer may consider vascular endothelial growth factor targeted therapy over immunotherapy.
32418885 Interestingly, iron chelation has been shown in vitro to suppress endothelial inflammation in viral infection, which is the main pathophysiologic mechanism behind systemic organ involvement induced by SARS-CoV-2, by inhibiting IL-6 synthesis through decreasing NF-kB. […] These agents could attenuate ARDS and help control SARS-CoV-2 via multiple mechanisms including: 1) inhibition of viral replication; 2) decrease of iron availability; 3) upregulation of B cells; 4) improvement of the neutralizing anti-viral antibody titer; 5) inhibition of endothelial inflammation and 6) prevention of pulmonary fibrosis and lung decline via reduction of pulmonary iron accumulation.
32425328 The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications.
32425360 Some of the mechanisms and conditions underlying endothelial dysfunction.A-human skin capillaries, visualized with high-resolution intravital color microscopy in the finger of a patient with obesity, metabolic syndrome and coronary artery disease.B- healthy control.
32427582 SARS-CoV-2 was demonstrated to infect type II, type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis.
32430627 A striking feature of COVID-19 pandemics is the high incidence of fatalities in advanced aged patients: this might be due to the prevalence of frailty and cardiovascular disease increase with age due to endothelial dysfunction and loss of endogenous cardioprotective mechanisms.
32430651 SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. […] There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation.
32431755 Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures.
32432162 Although the pathophysiologic mechanisms of STEMI in COVID-19 patients has not been clearly established, we hypothesize that interrelated pathogenetic factors, that we highlight in this report, can play a role in the development of STEMI, including plaque rupture secondary to systemic inflammation, increased pro-coagulants, endothelial dysfunction, impaired fibrinolysis and impaired oxygen utilization leading to demand/supply mismatch and myocardial ischemia.
32432519 We discuss the possible excess risk for COVID-19 infection in the context of the common conditions among shiftworkers, including nurses, doctors, and first responders, among others of high exposure to the contagion, of sleep imbalance and circadian disruption.Abbreviations: ACE2: Angiotensin-converting enzyme 2; APC: Antigen-presenting cells; CCL: Chemokine (C-C motif) ligand; CD+: Adhesion molecule expression; COVID-19: 2019 coronavirus disease; DCs: Dendritic cells; GH: Growth hormone; HPA: Hypothalamic-pituitary-adrenal; HSF: Heat shock factor; HSP70: Heat shock protein 70; HSP90: Heat shock protein 90; IL: Interleukin; INFγ: Interferon-gamma; LT/LB: T/B lymphocytes; MHC: Major histocompatibility complex; NK: Natural killer; RAAS: renin-angiotensin-aldosterone system; SARS: Severe acute respiratory syndrome; SCN: Suprachiasmatic nucleus;SD: Sleep deprivation; SNS: Sympathetic nervous system; Th1/Th2: T helper lymphocytes 1/2; TLR2/TLR4: Toll-like receptor 2/4; TNF-α: Tumor necrosis factor alpha; VEGF: Vascular endothelial growth factor.
32436629 Arterial thrombosis and venous thrombosis, variously attributed to long term patient immobilizations, inflammation, autoimmune reactions or endothelial cell damage to the blood vessels, have also been reported for COVID-19 infections (Bikdeli, 2020; Kollas, 2020).
32437596 The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes.
32445583 Immunohistochemistry for SARS-CoV/SARS-CoV-2 spike protein showed granular positivity in endothelial cells and epithelial cells of eccrine glands in both biopsies.
32447630 The ACE-2 receptor can be found in nervous system tissue and endothelial cells among the tissues of many other organs.Neurological complications have been observed with COVID-19.
32448674 Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke.
32450344 Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels.
32451317 Increasing evidence points to endothelial cell dysfunction as a key pathophysiological factor in severe coronavirus disease-19 (COVID-19), manifested by platelet aggregation, microthrombi and altered vasomotor tone. […] This may be driven by direct endothelial cell entry by the virus, or indirectly by activated inflammatory cascade. […] In this article, we propose that pre-existing endothelial dysfunction of microangiopathy, more commonly evident in diabetes and BAME groups, makes an individual vulnerable to the subsequent ‘endothelitis’ of COVID-19 infection.
32458111 To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening. […] Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission. […] This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.
32459524 Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, while alterations in cardiac structure and function and the pro-thrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients.
32459857 The haemostasis parameters we observed, including increased levels of von Willebrand factor and factor VIII, point towards a relevant involvement of endothelial cells in patients with severe COVID-19. […] We suggest that it is possible to hypothesise a spectrum of secondarily acquired, prothrombotic coagulopathy mediated by the endothelial interaction with SARS-CoV-2 as a cause of mortality in a subset of patients with a complicated clinical course of COVID-19.
32461141 COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. […] The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation and intravascular coagulation, and ultimately contributes to multiple organ failure and death.
32461554 In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects.
32476472 Diffuse pulmonary inflammation, endothelial inflammation and enhanced thrombosis are cardinal features of COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
32479921 The pathophysiologic mechanisms leading to acute kidney injury in COVID-19 infection are unclear but may include direct cytopathic effects of the virus on kidney tubular and endothelial cells, indirect damage caused by virus-induced cytokine release, and kidney hypoperfusion due to a restrictive fluid strategy.
32489024 Vascular endothelial growth factor receptor(VEGFR) and fibroblast growth factor receptor(FGFR) can inhibit the proliferation, activation and migration of fibroblasts by regulating the signal transduction pathway involved in the process of pulmonary fibrosis.
32490931 Small fibrinous thrombi in pulmonary arterioles and a tumefaction of endothelial were observed in the autopsies of fatal COVID-19 cases. […] Studies showed that the viral infection induces a vascular process in the lung, which included vasodilation and endothelial dysfunction. […] It is known that estradiol exerts a protective effect on endothelial function, activating the generation of nitric oxide (NO) via endothelial nitric oxide synthase.
32493030 Subsequent endothelial damage leads to transudation of plasma proteins, formation of hyaline membranes, and an inflammatory exudate, characteristic of ARDS.
32501731 As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack.
32502659 They may have a potential role as adjunctive therapy to mitigate the effects of endothelial dysfunction and dysregulated inflammation in patients with COVID-19 infection.
32504450 Human angiotensin-converting enzyme 2 (ACE2) widely expressing in arterial and venous endothelial cells and arterial smooth muscle cells has been identified as a functional receptor for SARS-CoV-2.
32505910 Herein, we present arguments underlying our hypothesis that IL-1β and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19.
32506364 Her predominantly thromboembolic presentation supports the concept of coronavirus infection of endothelial cells and hypercoagulability, or COVID-19 endotheliitis.
32508062 We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction.
32510978 Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. […] Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. […] Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. […] Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. […] This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.
32512122 The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and ‘endotheliitis’ in several organs including heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.
32514763 Coronavirus is a source of deep venous thrombosis (DVT) due to complications such as over-coagulation, blood stasis, and endothelial damage.
32519302 By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS.
32521760 These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19.
32523920 Coagulopathy is a common abnormality in patients with COVID-19 due to inflammation, hypoxia, immobilisation, endothelial damage and diffuse intravascular coagulation. […] SARS-CoV-2 is a novel infectious agent that causes COVID-19, which can manifest in several ways, affecting endothelial cells and most organs.There is growing evidence that SARS-CoV-2-mediated endothelial damage is due to direct viral injury and the systemic inflammatory response, possibly together with a cytokine storm.As endothelial damage can manifest as thromboembolic disease, such as pulmonary thromboembolism, appropriate anti-thrombotic preventive strategies should be followed, and proper screening and treatment for thromboembolic complications should be implemented.
32524732 Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation.
32526061 It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. […] The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications.
32527987 We speculate that ensuing downregulation of angiotensin-converting enzyme 2 expression may compound the risk conferred by pre-existing comorbidities and critically influence the pathogenesis of hemorrhagic stroke by elevating blood pressure and impairing cerebrovascular endothelial function.
32531539 OA with NPT treatment may have a role in optimization of bowel microcirculation and in the reduction of the endothelial and the systemic cytokine-related damage, improving also respiratory function.
32532805 The high rate of thrombotic complications associated with COVID-19 seems likely to reflect viral infection of vascular endothelial cells, which express the ACE2 protein that enables SARS-CoV-2 to invade cells. […] Various proinflammatory stimuli can promote thrombosis by inducing luminal endothelial expression of tissue factor (TF), which interacts with circulating coagulation factor VII to trigger extrinsic coagulation. […] It is therefore proposed that SARS-CoV-2 infection of endothelial cells evokes the expression of TF which is contingent on endosomal NADPH oxidase activation.
32539627 Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages.
32544615 Mesenchymal stem cells can suppress nonproductive inflammation and improve/repair lung cells including endothelial and alveolar cells, which damaged by COVID-19 virus infection.
32545518 Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells, we report the marked downregulation by PB125 of 36 genes encoding cytokines.
32546188 In severe SARS-CoV-2 infections, emerging data including recent histopathological studies have emphasized the crucial role of endothelial cells (ECs) in vascular dysfunction, immunothrombosis, and inflammation.Histopathological studies have evidenced direct viral infection of ECs, endotheliitis with diffuse endothelial inflammation, and micro- and macrovascular thrombosis both in the venous and arterial circulations. […] The pro-inflammatory cytokine storm, with elevated levels of interleukin-6 (IL-6), IL-2 receptor, and tumor necrosis factor-α, could also participate in endothelial dysfunction and leukocyte recruitment in the microvasculature. […] Ongoing trials directly and indirectly target COVID-19-related endothelial dysfunctions: i.e., a virus-cell entry using recombinant angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS-2) blockade, coagulation activation, and immunomodulatory therapies, such as anti-IL-6 strategies. […] Studies focusing on endothelial dysfunction in COVID-19 patients are warranted as to decipher their precise role in severe SARS-CoV-2 infection and organ dysfunction and to identify targets for further interventions.
32548259 By exploiting the endothelial dysfunction at sites of acute inflammation, these multidrug nanoparticles delivered the therapeutic agents in a targeted manner, conferring survival advantage to treated animals in models of endotoxemia.
32549531 A novel disease (Covid-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was responsible for thousands of hospitalizations for severe acute respiratory syndrome, with several cases of thrombotic complications due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis.
32551862 Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage and lung coagulopathy promoting endothelial dysfunction and microthrombosis.
32554340 Some aspects of the pathogenesis of the disease recall events occurring in Mg deficiency, such as a drop of T cells, increased plasma concentration of inflammatory cytokines, and endothelial dysfunction.
32554923 We posit that: (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.
32558075 It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell-death, hypoxia, and endothelial damage are involved.
32558198 To explore the coagulopathy and endothelial dysfunction in COVID-19 patients. […] Study analyzed clinical and biological profiles of patients with suspected COVID-19 infection at admission, including hemostasis tests and quantification of circulating endothelial cells (CECs). […] Curative anticoagulation could prevent COVID-19-associated coagulopathy and endothelial lesion.
32558620 Although thrombosis initiated by the innate immune system is hypothesized to limit SARS-CoV-2 dissemination, aberrant activation of this system can cause endothelial injury resulting in loss of thromboprotective mechanisms, excess thrombin generation, and dysregulation of fibrinolysis and thrombosis.
32558979 Vascular injury may be due to the direct damage of endothelial cells by the virus or may represents an epiphenomenon of a dysregulated host inflammatory responses triggered by the infection2 .
32559338 These include increased thromboembolism and vascular dysfunction (Lax et al, 2020; Menter et al, 2020; Wichmann et al, 2020), infection of endothelial cells (Varga et al, 2020), viral spread in different organs (Puelles et al, 2020), or the pathological mechanisms of lung injury (Ackermann et al, 2020; Schaller et al, 2020).
32560665 In this viewpoint, we summarize the relevance of thromboinflammation in COVID-19 and discuss potential mechanisms of endothelial injury as a key point for the development of lung and distant organ dysfunction, with a focus on direct viral infection and cytokine-mediated injury. […] Entanglement between inflammation and coagulation and resistance to heparin provide a rationale to consider other therapeutic approaches in order to preserve endothelial function and limit microthrombosis, especially in severe forms.
32561465 Heparin, clinically used as an anticoagulant, has also anti-inflammatory properties including binding of inflammatory cytokines, inhibition of neutrophil chemotaxis, protection of endothelial cells and a potential antiviral effect.
32561682 Three patients had endothelial reticular aggregates.
32561849 No endothelial cell infection was observed.
32562567 Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endothelialitis to fibrinoid necrosis and thrombosis. […] SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. […] Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy. […] Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID-19 chilblains and perhaps also in a group of patients severely affected by COVID-19 presenting with features of microangiopathic damage.
32568187 There is growing evidence that COVID-19 not only affects the lungs but beyond that the endothelial system. […] The combination of endothelial dysfunction with a generalized inflammatory state and complement elements may together contribute to the overall pro-coagulative state described in COVID-19 patients leading to venular as well as to arteriolar occlusions.
32568969 These therapies include immunomodulators (i.e. intravenous immunoglobulin, thymosin α-1, IL-6, tocilizumab, cyclosporine, thalidomide, fingolimod), Chinese medicines (i.e. glycyrrhizin, baicalin, Xuebijing), anti-vascular endothelial growth factors (bevacizumab), estrogen modulating drugs, statins and nutritional supplements (i.e. vitamin A, B, C, D, E and zinc).
32569879 We demonstrate how the complement system is able to activate the coagulation cascade and platelets, inhibit fibrinolysis and stimulate endothelial cells.
32576730 What appears to be constant in all skin biopsies was the presence of prominent dilated blood vessels with a swollen endothelial layer, vessels engulfed with red blood cells, and perivascular infiltrates, consisting mainly of cytotoxic CD8+ lymphocytes and eosinophils.
32580257 SARS-CoV-2 infects host cells by targeting the angiotensin-converting enzyme 2 (ACE2) receptor, which is present on endothelial cells in the lung, heart, kidney, and gastrointestinal tissue.
32581017 Representative sections of the COVID-19 victim’s lung showed: nuclear expression of p-STAT3 (Tyr 705) in many of the alveolar pneumocytes and in occasional endothelial cells; COX-2 expression in the alveolar pneumocytes; a relative paucity of CD8+ cytotoxic lymphocytes; absence of CD56+ NK lymphoid cells; abundance of intra-alveolar and alveolar interstitial CD163+ macrophages/monocytes; PD-L1 expression on occasional macrophages, focally on collections of alveolar pneumocytes, and on cells in the alveolar interstitium; and rare PD-1+ lymphocytes in similar regions as CD8+ lymphocytes.
32582936 In a retrospective study of 39 COVID-19 patients and 32 control participants in China, we collected clinical data and examined the expression of endothelial cell adhesion molecules by enzyme-linked immunosorbent assays. […] In conclusion, the increased expression of endothelial cell adhesion molecules is related to COVID-19 and disease severity and may contribute to coagulation dysfunction.
32583053 Herein, we report a case of a 64-year old woman with COVID19 infection who developed a PRES, and we suggest that it could be explained by the disruption of the blood brain barrier induced by the cerebrovascular endothelial dysfunction caused by SARS-CoV-2.
32583086 The high reported morbidity has been related to hypoxia and inflammation leading to endothelial dysfunction and aberrant coagulation in small and large vessels. […] This review addresses some of the pathways leading to endothelial derangement, such as complement, HIF-1α, and ABL tyrosine kinases.
32585364 In the light of the new clinical data obtained from COVID-19 patients, mechanisms such as cytokine storm, pulmonary and endothelial dysfunction, hypercoagulation that may render individuals with diabetes more vulnerable to COVID-19 will be discussed in the end.
32585699 Here, we provide an updated overview of the impact of tobacco/waterpipe (shisha) smoking and e-cigarette vaping on endothelial function, a biomarker for early, subclinical, atherosclerosis from human and animal studies. […] We discuss the impact of the toxic constituents of these products on endothelial function and subsequent CVD and we also provide an update on current recommendations, regulation and advertising with focus on the USA and Europe.
32586214 The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 is due to the ability of SARS-CoV-2 to invade endo¬thelial cells via angiotensin-converting enzyme 2 (ACE2), which is expressed on the endothelial cell surface. […] However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic compli¬cations such as deep vein thrombosis, pulmonary embolism and stroke.
32592919 Several authors suggested that cardiovascular diseases and diabetes mellitus are linked to endothelial dysfunction, and all of them are strictly related to aging. […] It is known that the activation of endothelial estrogen receptors increases NO and decreases ROS, protecting the vascular system from angiotensin II-mediated vasoconstriction, inflammation, and ROS production. […] In this context, the preservation of endothelial function and the mitigation of vascular inflammation are prominent targets, essential to reduce severe outcomes also in male older patients.
32294809 This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death.
32409501 They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis.
32593832 Several factors may increase intestinal permeability including direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction.
32594778 The inflammatory cascade induces endothelial activation and capillary leak, leading to circulatory collapse and shock. […] As endothelial dysfunction persists, there is activation of the clotting cascade and microvascular obstruction. […] Continued endothelial activation results in multi-organ failure, regardless of pulmonary tissue damage.
32600978 The haemostatic system acts in concert with inflammation, so that after inflammatory response various mediators activate the haemostatic system through endothelial dysfunction, platelet activation and coagulation promoting thrombosis, which is termed thromboinflammation.
32601125 It has been recently proposed that COVID-19 is an endothelial disease. […] Indeed, the COVID-19 virus binds to angiotensin-converting enzyme type 2 (ACE2), which is expressed in endothelial cells. […] ACE2 could be implicated in the production of reactive oxygen species (ROS) caused by endothelial dysfunction due to viral damage.
32607684 Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes.
32615987 Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels.
32619411 Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. […] To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19. […] We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. […] Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).
32621757 The latter might be partly attributed to the variation in VTE risk factors in COVID-19 patients including: (i) patients’ characteristics; (ii) hospitalization conditions and interventions; and (iii) SARS-CoV-2-specific factors (coagulopathy, endothelial injury/microthrombosis).
32622823 Systemic capillary leak syndrome is a rare disorder characterized by dysfunctional inflammatory response, endothelial dysfunction, and extravasation of fluid from the vascular space to the interstitial space leading to shock, hemoconcentration, hypoalbuminemia, and subsequent organ failure.
32627126 The accumulative evidences suggest that novel coronavirus, apart from its primary respiratory confinement, may also invade vascular endothelial cells of several systems including cerebral, cardio-pulmonary as well as renal microvasculature, modulating multiple visceral perfusion indices.
32629875 Angiotensin converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 and other coronaviruses, is a transmembrane protein expressed by lung alveolar epithelial cells, enterocytes, and vascular endothelial cells, whose physiologic role is to induce the maturation of angiotensin I to generate angiotensin 1-7, a peptide hormone that controls vasoconstriction and blood pressure. […] In this review, we provide the general context of the molecular and cellular mechanisms of SARS-CoV-2 infection with a focus on endothelial cells, describe the vasculopathy and coagulopathy syndromes in patients with SARS-CoV-2, and outline current understanding of the underlying mechanistic aspects.
32634813 This patient had ischemic injuries in different sites as well as venous thrombosis; hence, we speculate that Sars Cov2 could have a direct role in promoting vascular accidents since its receptor ACE2 is a surface protein also expressed by endothelial cells.
32639031 PAR1 activation also impacts on the actions of other cell types involved in COVID-19 pathobiology, including endothelial cells, fibroblasts and pulmonary alveolar epithelial cells.
32641481 Immunohistochemistry and immunofluorescence staining against serpentovirus nucleoprotein demonstrated that the virus infects not only a broad spectrum of epithelia (respiratory and alimentary epithelium, hepatocytes, renal tubules, pancreatic ducts, etc.), but also intravascular monocytes, intralesional macrophages, and endothelial cells.
32642005 Comparatively, ACE2 is expressed at low level by vascular endothelial cells of the heart and kidney but may also be targeted by the virus in severe COVID-19 cases.
32643664 Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point.
32643798 Complement deposition on endothelial cells and high blood C5a serum levels have been reported in COVID-19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA).
32645151 Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis.
32646061 Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others.
32647526 Viral neurotropism, endothelial dysfunction, coagulopathy and inflammation are plausible proposed mechanisms of CVD in COVID-19 patients.
32650197 Adenosine A2A receptors (A2AR), expressed by a wide range of immune cells, as well as endothelial cells and platelets, exert cAMP-mediated anti-inflammatory and anti-thrombotic effects that potentially could be highly protective in this regard.
32651579 In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19.
32654006 We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution.
32654082 Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19. […] • Endothelial dysfunction, platelet activation, hyperviscosity, and blood flow abnormalities due to hypoxia, immune reactions, and hypercoagulability lead to thrombogenesis in COVID-19.
32654359 Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels.
32657623 It is likely that multiple systems contribute to thrombosis in COVID-19 patients, such as activation of coagulation, platelet activation, hypofibrinolysis, endothelial cell dysfunction, inflammation, neutrophil extracellular traps, and complement.
32660065 SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. […] The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. […] Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. […] Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19.
32661947 Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED.
32662814 Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway and vascular endothelial growth factor signaling pathway.
32664116 Pathological specimens were analyzed with evidence of diffuse alveolar septum disruption, interstitium thickness, and infiltration of inflammatory cells with diffuse endothelial dysfunction and hemorrhagic thrombosis. […] Despite well-known pulmonary damages induced by the COVID-19, the late-phase histological changes include diffused peripheral vessels endothelial hyperplasia, in toto muscular wall thickening, and intravascular hemorrhagic thrombosis.
32664949 TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells.
32665039 To explore laboratory markers within participants with confirmed COVID-19: including circulating markers of host immune and endothelial activation in participant plasma and their correlation with disease severity and outcome TRIAL DESIGN: The HEROS study is a two-arm, parallel-group, individually randomized (1:1 allocation ratio), placebo controlled, participant and investigator-blinded, multi-site superiority trial of oral HCQ 400 mg taken once daily for 90 days as PrEP to prevent COVID-19 in health care workers at high risk of SARS-CoV-2 exposure.
32665934 Indeed, endothelial/microvascular damage to pulmonary capillaries seems to be the main trigger of the pneumonia.
32668062 The BBB is composed of highly specialized endothelial cells, pericytes, mast cells and astrocytes that form the neurovascular unit, which regulates BBB permeability and maintains the integrity of the CNS.
32668803 Lysosomotropic compounds affect prominent inflammatory messengers (e.g., IL-1B, CCL4, CCL20, and IL-6), cathepsin-L-dependent viral entry of host cells, and products of lysosomal enzymes that promote endothelial stress response in systemic inflammation.
32670517 Although the etiology of Kawasaki disease (KD) remains elusive, the available evidence indicates that the primum movens may be a dysregulated immune response to various microbial agents, leading to cytokine cascade and endothelial cell activation in patients with KD.
32671455 However, other causal factors can still be identified such as unrestricted angiotensin II action, the use of immunoglobulins, an increased production of adhesion molecules able to induce vascular inflammation and endothelial activation, complement stimulation, excessive production of neutrophil extracellular traps (NETs), and increased platelet count.
32672790 Excess soluble fms-like tyrosine kinase 1 (sFlt-1), a soluble inhibitor of the vascular endothelial growth factor pathway, has been demonstrated to promote endothelial dysfunction. […] Here we demonstrate that sFlt-1 plasma levels correlate with respiratory symptoms severity, expression of endothelial dysfunction biomarker and incidence of organ failure in COVID-19 patients.
32676039 We tried to summarize data reported in the last months from several Countries, highlighting that COVID-19 was characterized by cytokine storm (CS) and endothelial dysfunction in severely ill patients, where the progression of the disease was fast and fatal. […] Endothelial dysfunction was the fundamental mechanism triggering a pro-coagulant state, finally evolving into intravascular disseminated coagulation, causing embolization of several organs and consequent multiorgan failure (MOF).
32676824 Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]). […] We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. […] High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.
32679784 Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple components of the innate and adaptive immune system as well as endothelial membrane stability.
32681845 Inflammatory storm, uncontrolled inflammation-mediated endothelial injury and renin angiotensin system (RAS) dysregulation are the potential mechanisms.
32684080 COVID-19 can cause severe pneumonia, and neurological disorders, including stroke, the damage to the neurovascular unit, blood-brain barrier disruption, high intracranial proinflammatory cytokines, and endothelial cell damage in the brain. […] COVID-19 can activate mast cells, neurons, glial cells, and endothelial cells.
32685882 In severe cases, the acute systemic inflammatory response, coagulation activation, and diffuse endothelial damage may, in combination with hypoxia, immobilization, and underlying risk factors, result in potentially life-threatening venous and arterial thrombotic events.
32685886 SARS-CoV-2 replicates in TF-bearing epithelial and endothelial cells and may stimulate and integrate host cell TF, like HSV1 and other known coagulopathic viruses.
32687449 Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. […] Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome.
32691370 Expression of this receptor has been described in several types of cells, including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), which raises a concern that the virus may infect and damage the stem cell compartment.
32691699 Widespread systemic inflammation and procoagulant/hypercoagulable state, including thrombotic microangiopathy, endothelial dysfunction, bleeding disorder, and thrombosis are increasingly being witnessed in COVID-19.
32701690 What appears to be constant in all skin biopsies was the presence of prominent dilated blood vessels with a swollen endothelial layer, vessels engulfed with red blood cells, and perivascular infiltrates, consisting mainly of cytotoxic CD8+ lymphocytes and eosinophils.
32706411 This is due to the fact that the main axis of this disease is the endothelial compromise and the production of a “cytokine storm,” triggering multiple organ failure and death.
32708334 Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. […] In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction.
32712049 The viral infection initiates inflammatory responses leading to endothelial damage and coagulation cascade dysfnction.
32722927 Furthermore, systemic cytokine storm induced vascular endothelial injury, which extensively mediates hypercoagulability in blood vessels and disseminated intravascular coagulation.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32722979 T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. […] This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. […] COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases.
32735050 Severe pro-inflammatory and pro-thrombotic states with endothelial involvement have been reported associated with severe COVID-19 infection.
32735131 The SARS-CoV2 virus can directly infect immune and endothelial cells, leading to endothelial injury and dysregulation of the immune system.
32736027 COVID-19 accesses host cells via angiotensin-converting enzyme 2 protein, abundant in the lungs, which is also expressed by endothelial cells and is associated with important inflammatory syndrome and coagulopathy, leading to vascular lesions.
32739471 These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. […] Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS.
32740067 Retinal outpatient visits, new patient visits, intravitreal antivascular endothelial growth factor injections and in-office multimodal retinal imaging has seen a significant decline in utilization in the early phase of the pandemic.
32740069 They enable risk stratifying patients based on individual risk of vision-threatening diabetic retinopathy including diabetic macular edema (DME), and predicting which patients with DME best respond to antivascular endothelial growth factor therapy.
32741970 No ACE2 expression was detected in villous stroma, Hofbauer cells, or endothelial cells.
32742564 Mesenchymal stromal cells, endothelial progenitor cells, peripheral blood stem cells, and lung progenitor cells have been applied to clinical trials.
32744052 IL-1 causes endothelial dysfunction, the triggering factor of which may be of a different nature including pathogen infection. […] IL-1 causes platelet vascular thrombogenicity also on non-endothelial cells by stimulating the formation of thromboxane A2 which is released into the inflamed environment. […] IL-1 is the most important immune molecule in inducing fever, since it is involved in the metabolism of arachidonic acid which increases from vascular endothelial organs of the hypothalamus. […] Hence, IL-1 stimulates endothelial cell-leukocyte adhesion, and TxB2 production.
32745993 Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage.
32747391 We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19.
32748336 The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors.
32749712 We demonstrate maternal vascular malperfusion, with no fetal vascular malperfusion, as well as SARS-CoV-2 virus in chorionic villi endothelial cells, and also rarely in trophoblasts.
32750019 COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance.
32750108 There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19. […] We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients. […] A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications.
32752129 Endothelial dysfunction is a common feature between patients with PAH/CTEPH and COVID-19, leading to ventilation/perfusion mismatch, vasoconstriction, thrombosis and inflammation.
32754041 Viremia is observed in severe cases, suggesting that in addition to type II alveolar epithelial cells, many cell types, such as vascular endothelial cells, cardiomyocytes, renal tubular cells, neuronal cells, and lymphocytes, may be damaged.
32754823 We identified the chaperones that can putatively participate in molecular mimicry phenomena after SARS-CoV-2 infection, focusing on those for which endothelial cell plasma-cell membrane localization has already been demonstrated. […] We also postulate that post-translational modifications, induced by physical (shear) and chemical (metabolic) stress caused respectively by the risk factors hypertension and diabetes, might have a role in determining plasma-cell membrane localization and, in turn, autoimmune-induced endothelial damage.
32755395 This mode of posttranslational modification of ACE2 in vascular endothelial cells is causative of a pulmonary hypertension (PH)-protective phenotype. […] Cultured endothelial cells, mouse models, and specimens from patients with idiopathic pulmonary arterial hypertension were used to investigate the crosstalk between AMPK and MDM2 in regulating ACE2 phosphorylation and ubiquitination in the context of PH. […] Levels of MDM2 were increased and those of ACE2 decreased in lung tissues or pulmonary arterial endothelial cells from patients with idiopathic pulmonary arterial hypertension and rodent models of experimental PH. […] Moreover, ACE2-K788R overexpression in mice with endothelial cell-specific AMPKα2 knockout mitigated PH.
32755724 It is highly expressed in maternal-fetal interface cells, such as syncytiotrophoblasts, cytotrophoblasts, endothelial cells, and the vascular smooth muscle cells of primary and secondary villi.
32758257 Specifically, how systemic hyper-inflammation provoked by maladaptive innate immunity may impair neurovascular endothelial function, disrupt BBB, activate CNS innate immune signaling pathways, and induce para-infectious autoimmunity, potentially contributing to the CNS complications associated with SARS-CoV-2 infection.
32758869 Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19.
32758871 Our model predicts global vascular insult related to direct endothelial cell damage, vasoconstriction and thrombosis with a disease specific cytokine profile related to angiotensin II rather than “cytokine storm”.
32759013 Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). […] A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion.
32759504 Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures.
32762081 Postmortem studies have confirmed the high incidence of venous thromboembolism, but also notably revealed diffuse microvascular thrombi with endothelial swelling, consistent with a thrombotic microangiopathy, and inter-alveolar endothelial deposits of complement activation fragments.
32762135 This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19.
32762140 During the course of COVID-19, the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells. […] CD146 + circulating endothelial cells (CD146 + CECs) and their progenitors (CEPs) are increased in cardiovascular, thrombotic, infectious, and cancer diseases. […] CD146 + CECs and CEPs might be investigated as candidate biomarkers of endothelial damage in COVID-19 patients.
32762443 Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. […] This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. […] Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. […] Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples.
32763657 Human Coronavirus (HCoV) infection causes infiltration of inflammatory cells that cause excessive production of cytokines, proteases, coagulation factors, oxygen radicals and vasoactive molecules causing endothelial damage, disruption of fibrous cap and initiation of formation of thrombus.
32763660 COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. […] Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. […] ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. […] Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage.
32764118 Epidemiological data from the SARS-CoV-2 outbreak suggest sex differences in mortality and vulnerability; yet sex-dependent incidences of acute respiratory distress syndrome (ARDS) remain controversial and sex-dependent mechanisms of endothelial barrier regulation is unknown. […] Since stimulation of the Ang-(1-7)/Mas axis protects the endothelial barrier in acute lung injury (ALI), we hypothesised that increased Ang-(1-7)/Mas signalling may protect females over males in ALI/ARDS.Clinical data were collected from Charité inpatients. […] Endothelial permeability was assessed as weight change in isolated lungs and as trans-endothelial electrical resistance in vitroIn 734 090 Charité inpatients (2005-2016), ARDS had a higher incidence in men as compared to women. […] In vitro, estrogen increased Mas receptor expression and attenuated endothelial leak in response to thrombin; this effect was alleviated by Mas receptor blockade.Improved lung endothelial barrier function protects female mice from ALI-induced lung edema.
32775990 Kidney biopsy specimens showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in situ hybridization of viral infection of kidney cells.
32776617 SARS-CoV-2 enters the blood stream by breaching the blood-air barrier via the lung capillary adjacent to the alveolus, and then attaches to the angiotensin-converting enzyme II receptors on the endothelial cells. […] Once SARS-CoV-2 enters the blood stream, a cascade of events (Steps 1-8) unfolds including accumulation of angiotensin II, reactive oxygen species, endothelial dysfunction, oxidation of beta 2 glycoprotein 1, formation of antiphospholipid antibody complexes promoting platelet aggregation, coagulation cascade, and formation of cross-linked fibrin blood clots, leading to pulmonary emboli (PE) and large vessel strokes seen on angiographic imaging studies.
32777054 We then expose openly-available experimental repository data that demonstrate the gene for ACE2 lies in a novel cluster of interegulated genes on the X chromosome including PIR encoding pirin (quercetin 2,3-dioxygenase), and VEGFD encoding the predominantly lung-expressed vascular endothelial growth factor D. […] The five double-elite enhancer/promoters that are known to be operational, and shared read-through lncRNA transcripts, imply that ongoing SARS-CoV-2 infection will reduce host defences to reactive oxygen species, directly generate superoxide O2 - and H2O2 (a “ROS storm”), and impair pulmonary endothelial homeostasis.
32779733 Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS-CoV-2 protein, IL6, and caspase 3; SARS CoV-2 RNA was not seen.
32781796 In this systematic review, we focus on the functional role of arginine in the regulation of endothelial function and vascular tone.
  1. Results: The results of the present study suggest that COVID-19 infection can cause different forms of acute respiratory distress syndrome (ARDS), due to diffuse alveolar damage and diffuse endothelial damage. […] The data on Factor VIII discussed in this paper, although preliminary and limited in number, seem to suggest that the thrombogenicity of Sars-CoV2 infection might be linked to widespread endothelial damage.
32791568 This systemic form of COVID-19 may be due to inflammation and vascular endothelial cell injury. […] The vascular endothelial glycocalyx comprises glycoproteins and plays an important role in systemic capillary homeostasis maintenance. […] The endothelial glycocalyx is very thin in the pulmonary capillaries, where it is affected by gaseous exchange with the alveoli and the low intravascular pressure in the pulmonary circulation. […] Despite the clearly important roles of the glycocalyx in vascular endothelial injury, thrombosis, vasculitis, and inflammation, the link between this structure and vascular endothelial cell dysfunction in COVID-19 remains unclear.
32803146 Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction.
32807412 The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system.
32809158 Besides the respiratory involvement, COVID 19 patients frequently develop a pro-coagulative state caused by virus-induced endothelial dysfunction, cytokine storm and complement cascade hyperactivation.
32812049 The objective of this study was to investigate whether increased levels of circulating endothelial cells (CEC) might be associated with severe forms of COVID-19. […] Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. […] Altogether, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.
32816230 The following cell types expressed ACE2: basal, apical, goblet, minor salivary, and endothelial cells.
32818801 SARS-CoV-2 antigens, RNA and/or particles morphologically consistent with coronavirus were identified in villous syncytiotrophoblast, endothelial cells, fibroblasts, in maternal macrophages, and in Hofbauer cells and fetal intravascular mononuclear cells.
32822775 We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). […] Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress.
32825011 It is proposed that the bioactive lipid, arachidonic acid (AA, 20:4 n-6), can inactivate severe acute respiratory syndrome(SARS-CoV-2), facilitate M1 and M2 macrophage generation, suppress inflammation, prevent vascular endothelial cell damage, and regulate inflammation resolution processes based on the timely formation of prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) based on the context.
32825713 Caveolae are flask-shaped invaginations of the plasma membrane found in numerous cell types and are particularly abundant in endothelial cells and adipocytes. […] The goal of this review is to discuss the most recent studies related to the role of caveolae and caveolins in endothelial cells. […] We also address how caveolae and caveolins control endothelial cell metabolism, a central mechanism involved in migration proliferation and angiogenesis. […] Finally, as regards the emergency caused by COVID-19, we propose to study the caveolar platform as a potential target to block virus entry into endothelial cells.
32825954 The interference on renin-angiotensin-aldosterone system (RAAS) activation, heme formation, and the immune response is responsible for infection diffusion, endothelial dysfunction, vasoconstriction, oxidative damage and releasing of inflammatory mediators.
32826331 Our in vitro data indicate that endothelial IL-6 trans-signaling formed an inflammation circuit for robust IL-6, IL-8, and MCP-1 production and promoted PAI-1 production; additionally, an IL-6 signaling blockade by the human monoclonal antibody tocilizumab blunted endothelial cell activation. […] Thus, the present study highlights the crucial role of IL-6 signaling in endothelial dysfunction during bacterial infection and COVID-19.
32828653 Anticoagulation may be a challenge in coronavirus disease 2019 (COVID-19) extracorporeal membrane oxygenation due to endothelial injury and dysregulation of coagulation, which may increase the risk of thrombotic and bleeding complications.
32829467 In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome.
32829885 Thrombotic complications due to COVID-19 are likely to occur due to a pro-coagulant pattern encountered in some of these patients or to a progressive endothelial thrombo-inflammatory syndrome causing microvascular disease. […] Specifically, this review will show complications related to thromboembolism due to a pro-coagulant pattern from those likely related to an endothelial thrombo-inflammatory syndrome.
32831324 It is possible that cutaneous blood vessels endothelial damage, as well as the effect of circulating inflammatory mediators produced in response to the virus, are the cause of skin involvement.
32835015 This has also been described in a proposed mechanism for PRES, where elevated inflammatory markers result in endothelial injury causing interstitial fluid extravasation typical of PRES.
32835124 Its cleavage action is an essential activation step for the endothelial pathogenicity of several viruses including SARS-CoV-2. […] This Furin-mediated endothelial tropism seems to underlie the multi-organ system involvement of COVID-19; which is a feature that was not recognized in the older versions of coronaviridae.
32837586 The design of the microfluidic device consists of two orthogonal channels: an inlet that serves as a model blood vessel, and a bleeding channel to model hemostatic plug formation at sites of compromised endothelial barrier function.
32838054 GPCR-G protein signaling at the plasma membrane causes endothelial barrier disruption and also cross-talks with growth factor receptors to promote proinflammatory signaling.
32838215 Evidence has accumulated that ANP administered to pulmonary endothelial cells, isolated lungs, and patients suffering from ARDS reduces endothelial damage and preserves the endothelial barrier, thereby reducing pulmonary edema and inflammation.
32838559 A distinction was made between urgent procedures: any trauma repairment, trabeculectomy/drainage implant for glaucoma, any operation for rhegmatogenous retinal detachment (RRD) repair, pars plana vitrectomy (PPV) for vitreous hemorrhage (VH), macular hole, or retained lens fragments; elective procedures: corneal transplant, phacoemulsification for cataract extraction, silicone oil removal, and PPV for epiretinal membrane; and intravitreal injections (either anti-vascular endothelial growth factor [VEGF] or dexamethasone) to treat exudative maculopathies.
32845609 Neuronal and glial cells and endothelial cells in the central nervous system also express ACE2.
32847471 Post-mortem examinations of patients’ tissues have confirmed direct viral endothelial infection within several organs. […] While there have been advances in single-cell RNA sequencing, endothelial cells across various vascular beds express low or undetectable levels of those touted SARS-CoV-2 entry factors. […] Emerging studies postulate alternative pathways and the apicobasal distribution of host cell surface factors could influence endothelial SARS-CoV-2 entry and replication. […] Finally, we provide experimental considerations such as endothelial polarity, cellular heterogeneity in organoids and shear stress dynamics in designing cellular models to facilitate research on viral-induced endothelial dysfunctions.
32847626 To investigate the effect of continuous infusion of the potential endothelial cytoprotective agent prostacyclin (Iloprost) 1 ng/kg/min vs. placebo for 72 hours on pulmonary endotheliopathy in mechanically ventilated COVID-19 patients. […] A multicenter, randomized (1:1, active: placebo), blinded, parallel group exploratory trial PARTICIPANTS: Inclusion criteria are: Adult patients (>18 years); Confirmed COVID-19 infection; Need for mechanical interventions; Endothelial biomarker soluble thrombomodulin >4ng/ml.
32848776 Endothelial barrier degradation and capillary leakage contribute to alveolar cell damage.
32849623 The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury.
32852539 Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. […] These data suggest a mechanism of pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.
32852642 To review current literature on endothelial dysfunction with previous coronaviruses, and present available data on the role of endothelial dysfunction in coronavirus disease-2019 (COVID-19) infection in terms of pathophysiology and clinical phenotype RECENT FINDINGS: Recent evidence suggests that signs and symptoms of severe COVID-19 infection resemble the clinical phenotype of endothelial dysfunction, implicating mutual pathophysiological pathways. […] Dysfunction of endothelial cells is believed to mediate a variety of viral infections, including those caused by previous coronaviruses. […] Experience from previous coronaviruses has triggered hypotheses on the role of endothelial dysfunction in the pathophysiology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which are currently being tested in preclinical and clinical studies. […] Endothelial dysfunction is the common denominator of multiple clinical aspects of severe COVID-19 infection that have been problematic for treating physicians.
32853434 The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.
32853989 Here, we summarise potential beneficial, non-anticoagulant mechanisms underlying treatment of COVID-19 patients with heparin/LMWH, which include: (i) Inhibition of heparanase activity, responsible for endothelial leakage; (ii) Neutralisation of chemokines, and cytokines; (iii) Interference with leukocyte trafficking; (iv) Reducing viral cellular entry, and (v) Neutralisation of extracellular cytotoxic histones.
32855182 The above findings raise the possibility of stroke related to mechanisms induced by the COVID-19 infection itself, including a hypercoagulable state and/or endothelial damage.
32863034 With a high safety profile, EPO promotes the production of endothelial progenitor cells and reduce inflammatory processes through inhibition of the nuclear factor-κB (NF-κB) and JAK-STAT3 signaling pathways.
32864934 The SARS-CoV2 enters human cells through the spike protein binding to angiotensin-converting enzyme 2 (ACE2), which is important to cardiovascular modulation and endothelial signaling.
32865603 Vasculitis, endothelial damage, thromboembolic events and organ failure are accompanied by a massive cytokine response.
32871306 The most reliable hypothetical pathogenetic mechanism for CV complications and cardiac injury in severe COVID-19 patients appears to be a sustained endothelial dysfunction, caused by the interplay of inflammation and coagulation.
32872395 The precise mechanisms remain a matter for further investigation; however, we may assume that endothelial NO synthase, haemoglobin and endothelium-derived hyperpolarising factor are deeply involved in the increase of intravascular NO.
32876900 Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke.
32877502 Animal models demonstrating end-organ protection in C3 deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear.
32879413 Ultrastructurally, small vessels showed basal membrane reduplication and significant endothelial swelling with cytoplasmic vacuolization.
32880032 Hydroxychloroquine has endothelial stabilizing and anti-thrombotic effects.
32880906 However, Colmenero and colleagues were able to detect SARS-CoV-2 in endothelial cells of cutaneous chilblain lesions by immunohistochemistry methods in 7 pediatric patients with negative nasopharyngeal swabs.
32881062 The resulting endothelial dysfunction further induces fibrosis and coagulopathy.These disturbancescan generatesevere respiratory distress syndrome (ARDS) that canprogress into respiratory and circulatory failure.
32881285 Endothelial VWF is stored in cell-specific secretory granules, Weibel-Palade bodies (WPBs), organelles generated in a wide range of lengths (0.5-5.0 µm). […] WPB size responds to physiological cues and pharmacological treatment, and VWF secretion from shortened WPBs dramatically reduces platelet and plasma VWF adhesion to an endothelial surface. […] Using a microscopy approach coupled to automated image analysis, we measured the size of WPB bodies in primary human endothelial cells treated with licensed compounds for 24 hours.
32882706 This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease. […] Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. […] The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic.
32882720 The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis.
32883116 Myocardial, lung and hepatorenal injury in patients with COVID-19 could be due to cytokine storm, hypoxic injury, or/and direct endothelial/vascular injury.
32883169 The prothrombotic coagulopathy mediated by the endothelial interaction with SARS-CoV-2 may also have role in unfavourable prognosis in COVID-19.
32883529 Recent articles have reported elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased patients with coronavirus 2019 (COVID-19).
32885463 One hypothesis is that progressive endothelial damage from the virus leads to microvascular thrombosis.
32889638 The realization that much of the consequences of such immune mimicry may play out on the plasma membrane of vascular endothelial cells raised the specter of autoimmune-induced vascular endothelial damage in multiple organs.
32889957 To report a case of acute corneal endothelial graft rejection with concurrent onset of coronavirus disease 2019 (COVID-19) symptoms. […] A 31-year-old African American female with a history of asthma, sleep apnea, obesity (BMI of 40), and bilateral keratoconus was noted to have acute corneal endothelial graft rejection three months after uncomplicated penetrating keratoplasty (PKP) of the left eye.
32892505 It is unknown whether this is due to a generalized humoral prothrombotic state or endothelial factors such as inflammation and dysfunction. […] Tissue plasminogen activator (tPA), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor (VEGF) were significantly increased in the critical versus noncritical patients. […] Importantly, disease severity did not increase thrombin generation (including thrombin-antithrombin complexes and prothrombin fragment 1 + 2) when comparing both cohorts; counter-intuitively critical patients were hypocoaguable. tPA, TFPI and VEGF were increased in critical patients, which are hypothesized to reflect endothelial dysfunction and/or contribution of heparin (which may cause endothelial TFPI/tPA release).
32895985 Prior studies have shown the presence of immunohistochemical staining for the SARS-CoV-2 spike protein (SP) in endothelial cells and eccrine epithelium of acral perniosis classified as “COVID toes.” […] Three of six cases showed positive immunohistochemical labeling of endothelial cells, with one of three cases with sufficient depth also having labeling of eccrine glands, using an anti-SP SARS-CoV-2 antibody. […] While the gold standard for detection of SARS-CoV-2 in tissue sections has yet to be determined, the detection of SARS-CoV-2 SP alone without spike RNA suggests that cleaved SP may be present in cutaneous endothelial cells and eccrine epithelium, providing a potential pathogenetic mechanism of COVID-19 endotheliitis.
32899833 In particular, cardiovascular (CV) cells (e.g., endothelial cells, cardiomyocytes) could be directly infected and indirectly disturbed by systemic alterations, leading to hyperinflammatory, apoptotic, thrombotic, and vasoconstrictive responses.
32900740 The endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism.
32903111 The blood-brain barrier (BBB), which protects the CNS from pathogens, is composed of specialized brain microvascular endothelial cells (BMECs) joined by tight junctions and ensheathed by pericytes and astrocyte endfeet. […] This article focuses on the structural and functional changes that occur in the three main components of the BBB (endothelial cells, astrocytes, and pericytes) in response to infection with neurotropic viruses transmitted by hematogenous routes, and also briefly describes the supportive effect of three cells on the BBB under normal physiological conditions.
32903391 Hypoxia, endothelial cell damage, and the different impacts of different ventilatory strategies may all lead to increased stress and strain, potentially exacerbating the inflammatory response and leading to a complex interaction between the lungs and the brain.
32903640 The majority of the dysfunctions mentioned above are often associated with endothelial deterioration, indicating that endothelium can be the target of SARS-CoV2.
32904031 Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms. […] Daily blood coagulation and thrombotic factor profiling with immunoassays and in vitro experiments on human pulmonary microvascular endothelial cells. […] Surface hyaluronic acid removal from human pulmonary microvascular endothelial cells with hyaluronidase treatment resulted in depressed nitric oxide, an instigating mechanism for platelet adhesion to the microvascular endothelium. […] Thrombosis profiling identified endothelial activation and glycocalyx degradation in coronavirus disease 2019 positive patients. […] Our data suggest that medications to protect and/or restore the endothelial glycocalyx, as well as platelet inhibitors, should be considered for further study.
32908843 COVID-19 is a contagious disease caused by SARS-CoV-2 that attacks endothelial cells and most organs, resulting in different manifestations and clinical scenarios.Point-of-care ultrasound in the emergency room including lung ultrasound (LUS) and focused echocardiography (FECHO) can be useful in identifying pulmonary and vascular manifestations of COVID-19 disease during the current pandemic.Characteristic LUS signs suggesting bilateral interstitial pneumonia in addition to signs of acute right ventricular strain suggesting pulmonary embolism on FECHO raised the suspicion of COVID-19 infection in our patient.
32913304 With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. […] We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner.
32914775 It is important to determine whether the interferon immune response in some subjects can be the cause of both the low viremia and the endothelial damage so localized in the acral-site, as happens in other models of diseases (chilblain-lupus like).
32917441 Coronavirus disease 2019 (COVID-19) is associated with endothelial inflammation and a hypercoagulable state resulting in both venous and arterial thromboembolic complications.
32918295 Most severe COVID-19 cases present low lymphocytes counts and high leukocytes counts, and accumulated evidence suggests that in a subgroup of patients presenting severe COVID-19, there may be a hyperinflammatory response driving a severe hypercytokinaemia which may be, at least in part, signalling the presence of an underlying endothelial dysfunction. […] Following this rationale, we hypothesized that NLR, as a marker of endothelial dysfunction, may be useful in identifying patients with a poor prognosis in hospitalized COVID-19 cases.
32918409 This infection causes a prothrombogenic state by interplay of inflammatory mediators, and endothelial, microvascular, and possible hepatic damage and tissue tropism of the virus.
32918567 The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the pneumocytes, immune cells, and vascular endothelial cells. […] In addition to the endothelial damage, SARS-CoV-2 also can cause vasculitis and presents as a systemic inflammatory vascular disease. […] The endotheliopathy due to direct endothelial infection with SARS-COV-2 and the indirect damage caused by inflammation play the predominant role in the development of CAC.
32918938 COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction.
32919938 Systemic vascular endothelial inflammation and thrombocytopenia are potential consequences as well.
32920092 Results indicate a dominant hyperinflammatory milieu in the circulation and vascular endothelial damage markers within patients with COVID-19, and strong biomarker association with patient response as measured by Ordinal Scale.
32920756 We can speculate that IA might have the function of restoring a functional vascular plexus consequently to extensive endothelialitis and alveolar capillary micro-thrombosis observed in Covid-19. […] Anti-Vascular endothelial growth factor (anti-VEGF) strategies are currently investigated for treatment of severe and critically ill Covid-19 patients, but also FGF2, and its expression and/or signaling, might represent a promising target.
32920964 Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment.
32922301 TNF alpha can, through Rho-kinase, disintegrate the endothelial and epithelial cytoskeleton, and thus break up intercellular tight junctional proteins, breaching the intercellular barrier, which prevents flooding of the interstitial and alveolar spaces with fluid.
32924567 Coronavirus-2019 (COVID-19) predisposes patients to arterial and venous thrombosis commonly complicating the clinical course of hospitalized patients and attributed to the inflammatory state, endothelial dysfunction, platelet activation and blood stasis.
32926931 Exaggerated pulmonary vascular response to hypoxia may be related to endothelial dysfunction in hypoxia susceptible. […] Endothelial dysfunction in Group 2 resulted in reduced vascular compliance leading to elevation of mean blood pressure on acute hypoxia exposure. […] BNP showed a positive correlation with endothelial dysfunction in Group 2 and has been linked to pre-diabetic disorder (HbA1c 6 ± 0.44%) and may additionally represent a lower cross-sectional area of vascular bed related to vascular remodeling mediated by chronic hypoxia. […] Hypoxia susceptibility in healthy individuals may be related to endothelial dysfunction that limits vascular compliance during hypoxic stress. […] BNP level showed positive correlation with HbA1c (r = 0.49, p = 0.04) and negative correlation with delta pO2 (r = -0.52, p = 0.04) can predict reduced microvascular compliance due to endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals.
32930095 Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function.
32930394 In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). […] Pneumocytes but not endothelial cells also expressed TMPRSS2.
32936400 This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells.
32937949 These receptors are highly expressed in heart, lungs, respiratory tract epithelium, endothelial cells and brain.
32938758 Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions.
32943233 Autopsies commonly show arterial thrombosis and severe endothelial damage. […] Endothelial damage, which can play an early and central pathogenic role in ARDS and thrombosis, activates the lectin pathway of complement. […] At baseline and during treatment, circulating endothelial cell (CEC) counts and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were assessed. […] Narsoplimab may be an effective treatment for COVID-19 by reducing COVID-19-related endothelial cell damage and the resultant inflammation and thrombotic risk.
32944087 SARS-CoV-2 binds to the angiotensin-converting enzyme 2 receptor, which is abundantly expressed in vascular endothelial cells and damages these cells.
32944185 EV treatment resulted in: (1) attenuation of inflammation (reduction of pro-inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production).
32945096 It is well-known that VWF promotes neutrophil recruitment to endothelial surfaces under low-shear conditions and supports neutrophil extravasation towards inflamed tissues1 .
32945111 The identification of additional mechanisms involved in the endothelial damage as that described by Richardson et al. [1] mediated by the p38 MAPK pathway, which is upregulated as a result of the binding of SARSCoV2 on ACE2 receptors on the surface of endothelial cells and, in turn, activates the transcription of the proinflammatory cytokines.
32945158 The local inflammatory response in the lung that occurs after exposure to SARS-CoV-2 is due to a complex network of activated inflammatory innate immune cells and structural lung cells such as bronchial epithelial cells, endothelial cells and fibroblasts. […] In addition, endothelial cells which control leukocyte traffic through the expression of adhesion molecules are also able to amplify leukocyte activation by generating interleukin (IL)-1, IL-6 and CXC chemokines.
32946915 Endothelial dysfunction plays an important role in the coagulation disorders via increased generation of the thrombin and stops fibrinolysis further leads to hypercoagulopathy. […] Along with that endothelial dysfunction activates the complement system pathways and contributes to the acute and chronic inflammation via cytokine storm with the production of the cytokines and chemokines, coagulation in different organs such as lung, brain, liver, heart, kidney and further leads to multi-organ failure.
32947478 The pathogenesis of COVID-19 has not been completely elucidated, but the virus is known to cause excessive inflammation, endothelial injury, hypoxia, and disseminated intravascular coagulation, all of which contribute to thrombosis formation.
32947927 The proposed pathophysiological mechanisms of myocardial impairment include invasion of SARS-CoV-2 virus via angiotensin-converting enzyme 2 to cardiovascular cells/tissue, which leads to endothelial inflammation and dysfunction, de-stabilization of vulnerable atherosclerotic plaques, stent thrombosis, cardiac stress due to diminish oxygen supply and cardiac muscle damage, and myocardial infarction.
32949574 Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19).
32949577 Twenty-seven cytokines were assessed: interleukin (IL)-1b, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor basic, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein, monocyte chemo-attractant protein-1, macrophage inflammatory protein (MIP)-1a, MIP-1b, platelet-derived growth factor (PDGF), regulated on activation normal T cell expressed and secreted, tumor necrosis factor-α and vascular endothelial growth factor (VEGF).
32953201 This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells.
32955690 Endothelial cell involvement with COVID-19 has been shown in the lung, heart, kidney, intestine and brain with histopathological evidence of endotheliitis and vasculitis.
32963216 BACKGROUND Recent studies demonstrated evidence of coagulation dysfunction in hospitalized patients with severe coronavirus disease 2019 (COVID-19) due to excessive inflammation, hypoxia, platelet activation, endothelial dysfunction, and stasis.
32965455 None of the cases progress to stage III, and all patients had remission of symptoms, with 100% survival. the process of endothelial dysfunction in COVID-19 involves disseminated thrombosis, initially microvascular and later expansion into larger vessels.
32967797 We review the mechanism of the high thrombus burden, which may be driven by the significant cytokine storm, endothelial dysfunction, increase risk of coronary plaque rupture and hypercoagulability.
32967859 Interestingly, vascular changes are frequently observed in association with DAD, which include severe endothelial injury/endothelialitis, hemorrhage, and thrombotic and microangiopathic vasculopathy.
32968645 Then, we speculated that the virus not only attacked alveolar epithelial cells, but also affected pulmonary vascular endothelial cells.
32969233 Endothelial-specific molecule 1 (endocan) plays a role in vascular pathology.
32972126 It is known that SARS-CoV-2 infects the host through the cell surface receptor of angiotensin-converting enzyme 2 (ACE2), which is expressed in multiple organs, and in the arterial and venous endothelial cells.
32973666 Large vessel disease with ESUS was common suggesting an increased risk of coagulopathy and endothelial dysfunction as a potential etiology.
32974916 Dear Editor, Recalcati et al. conclude that chilblain-like lesions (CLLs) are part of the spectrum of COVID-19 based on reports of SARS-CoV-2 in endothelial cells of skin biopsies assessed by immunohistochemistry and electron microscopy (EM).1 Nevertheless, the conclusion does not seem to be adequately supported by the data.
32980620 Post-mortem examinations show severe endothelial injury and widespread thrombotic microangiopathy in the pulmonary vasculature.
32981023 The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could interact with angiotensin-converting enzyme 2 (ACE2) in the endothelial, neural, and glial cells.
32983831 Endothelial cell involvement with COVID-19 has been shown in the lung, heart, kidney, intestine and brain with histopathological evidence of endotheliitis and vasculitis.
32991843 Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens.
32992810 Recent reports suggest that SARS-CoV-2, unlike other related viruses, infects and replicates within endothelial cells, which may explain a significant portion of the observed clinical pathology. […] Likewise, mounting evidence associates vascular and endothelial cell dysfunction with increased mortality. […] This review focuses on understanding how endothelial cell pathology is caused by SARS-CoV-2 at the molecular and cellular levels and how these events relate to COVID-19. […] A detailed examination of current knowledge regarding canonical inflammatory reaction pathways as well as alteration of endothelial cell-derived exosomes and transdifferentiation by SARS-CoV-2 is included in this assessment. […] Additionally, given an understanding of endothelial contributions to COVID-19, potential therapeutic aims are discussed, particularly as would affect endothelial function and pathology.
32993497 Lack of H2S-induced persulfidation of the KATP channels of leucocytes causes adhesion and release of the inflammatory cytokines, lung infiltration and systemic endothelial damage with hyper-coagulability.
32998398 The profound coagulation changes in COVID-19 seem to be linked to inflammation-related events and severe endothelial cell injury.
33000526 Additionally, COVID-19-induced endothelial damage helped to develop exaggerated hemorrhagic necrosis.
33002827 Vascular endothelial activation is pivotal for the pathological development of various infectious and inflammatory diseases. […] Therapeutic interventions to prevent endothelial activation are of great clinical significance to achieve anti-inflammatory strategy. […] The aim of this study was to investigate the effect and mechanism of rhamnocitrin (RH), a flavonoid extracted from Nervilia fordii, on LPS-induced endothelial activation. […] The in vitro endothelial cell activation model was induced by LPS in human umbilical vein endothelial cells (HUVECs). […] RT-PCR, Western blot, fluorescent probe and immunofluorescence were conducted to evaluate the effect and mechanism of RH against endothelial activation. […] The present study identifies RH as a potent inhibitor of endothelial activation. […] Since vascular endothelial activation is a pivotal cause of excessive cytokine production, leading to cytokine storm and severe pathology in infectious diseases such as SARS and the ongoing COVID-19 pneumonia disease, RH might suggest promising therapeutic potential in the management of cytokine storm in these diseases.
33003119 In addition, the modulation of endothelial function, the down-regulation of renin, angiotensin-converting-enzyme (ACE) and angiotensin genes and the up-regulation of ACE2 expression is still an area of research.
33004712 Indeed, COVID-19 is characterized by an abnormal inflammatory response resembling a cytokine storm, which is associated to endothelial dysfunction and microvascular complications. […] Medical ozone rationale in COVID-19 is the possibility of contrasting endothelial dysfunction, modulating the immune response and acting as a virustatic agent.
33005541 As COVID-19 patients are commonly having clotting disorders, endothelial and organ dysfunction, coagulopathy, and liable for pulmonary thromboembolism (PTE), it is important to select those COVID-19 patients who are at higher risk of PTE, and practice CT pulmonary angiography (CTPA) for the diagnosis of PTE, especially in case of significant increase of D-dimer values.
33005549 Diffuse endothelial injury and hypercoagulability play a pivotal role in recurrent thromboembolic events despite the anticoagulation. […] Therapeutic anticoagulation may be considered for severe COVID-19 patients and patients with important comorbidities or pre-existing endothelial dysfunction.
33009246 As both Spike protein and vascular endothelial growth factor-A (VEGF-A) - a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling.
33011274 The systemic inflammatory response syndrome that results from sepsis ultimately leads to degradation of the endothelial glycocalyx and subsequently increased vascular leakage. […] Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19.
33011887 Moreover, the organ failure may be induced by the cytokine storm, a result of increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs.
33014208 This high severity is dependent on a cytokine storm, most likely induced by the interleukin-6 (IL-6) amplifier, which is hyper-activation machinery that regulates the nuclear factor kappa B (NF-κB) pathway and stimulated by the simultaneous activation of IL-6-signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling in non-immune cells including alveolar epithelial cells and endothelial cells.
33015130 Next, we review how Se might be beneficial via restoration of host antioxidant capacity, reduction of apoptosis and endothelial cell damages as well as platelet aggregation.
33016027 In microorganism infections, the release of IL-1 macrophage acts on adhesion molecules and endothelial cells leading to hypotension and septic shock syndrome.
33017906 COVID-19 is also increasingly being recognized as a vascular disease, with several studies noting prominent systemic endothelial dysfunction. […] The pathogenesis of endothelial dysfunction may also be linked to COVID-19-mediated metabolic and inflammatory effects. […] This paper will explore the hypothesis that exercise may be a useful adjuvant in a setting of COVID-19 management/rehabilitation due to its effects on PPARα and vascular endothelial function.
33019920 The mechanisms exerted by SARS-CoV-2 that impairs hemostatic balance include endothelial injury, inflammation, activation of the immune and complement systems.
33019935 In a supposed preliminary pathogenetic model, SARS-CoV-2 plays a direct role in triggering widespread microthrombosis and microvascular inflammation, because it is able to induce transient aPL, endothelial damage and complement activation at the same time.
33021087 The higher expression of Angiotensin-converting enzyme 2 in the oral cavity and in endothelial cells might be responsible for oral manifestation and the major report of signs and symptoms in the occidental countries.
33021572 We investigated the microcirculatory, endothelial and inflammatory responses in critically ill COVID-19 patients and compared them to a group of patients with septic shock in a prospective observational case control study. 30 critically ill patients with COVID-19 were compared to 33 patients with septic shock.Measurements of sublingual microcirculatory flow using Incident Dark Field (IDF) video-microscopy and serial measurements of IL-6 and Syndecan-1 levels were performed. […] There was no evidence of significant sublingual microcirculatory impairment, widespread endothelial injury or marked inflammatory cytokine release in this group of critically ill COVID-19 patients.
33021761 An increase in cerebral basal blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in central nervous system and this can be evaluated as a result of endothelial dysfunction.
33022712 The pathophysiologic mechanisms of AKI in COVID-19 are thought to be multifactorial including systemic immune and inflammatory responses induced by viral infection, systemic tissue hypoxia, reduced renal perfusion, endothelial damage and direct epithelial infection with Severe Acute Respiratory Syndrome Coronavirus 2.
33022818 Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI.
33023500 The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy.
33023681 We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity.
33023738 Prolonged hypoxaemia, consumption coagulopathy, and endothelial disruption are the likely pathological drivers and reflect disease severity in this patient cohort.
33023827 Moreover, there is convincing preliminary evidence linking microbiota-gut-liver axis perturbations, proinflammatory status, and endothelial damage in noncommunicable preventable diseases with coronavirus disease 2019 (Covid-19) severity.
33024951 In light of current evidence regarding endothelium abnormalities related to COVID-19, this extreme case of catastrophic thrombotic syndrome suggests that COVID-19 can induce severe arterial thrombosis following intense endothelial activation.
33026628 It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed.
33032170 Vascular endothelial dysfunction can potentially activate coagulation cascade eventually resulting in thrombosis. […] ACE2 has proven role in the maintenance of endothelial integrity inside the vessels. […] Existing in situ evidence for SARS-CoV-1 (the causative agent for SARS pandemic of 2002, which shared ACE2 as cell entry receptor) suggested that virus binding can downregulate ACE2, thus can induce endothelial dysfunction.
33032965 In atherosclerosis patients, vascular endothelial dysfunction is commonly observed alongside damage of the vascular endothelial glycocalyx, an extracellular matrix bound to and encapsulating the endothelial cells lining the blood vessel wall. […] Interestingly, these comorbidities and risk factors are consistent with the pathophysiology that causes vascular endothelial glycocalyx damage. […] Notably, SARS-CoV-2, the causative virus of COVID-19, binds to ACE2, which is abundantly present not only in human epithelia of the lung and the small intestine, but also in vascular endothelial cells and arterial smooth muscle cells. […] Moreover, COVID-19 can induce severe septic shock, and sepsis can easily lead to systemic degradation of the vascular endothelial glycocalyx. […] In the current review, we propose new concepts and therapeutic goals for COVID-19-related vascular endothelial glycocalyx damage, based on previous vascular endothelial medicine research.
33033561 Multipotent MSCs are able to differentiate into different types of cells of mesenchymal origin, including alveolar epithelial cells, lung epithelial cells, and vascular endothelial cells, which are severely damaged in the course of COVID-19 disease.
33035434 Recent evidence points to the critical contributions of EVs to the pathogenesis of vascular endothelial barrier dysfunction during inflammatory response to injury or infection.
33035967 One of the therapeutic effects of GCs is stability of vascular endothelial barrier and decreasing tissue edema.
33036853 SARS-CoV-2 infection is known to cause a significant inflammatory response, as well as invasion of vascular endothelial cells, resulting in endothelial dysfunction.
33037393 The recruitment and subsequent activation of innate immune cells within an infected lung drives the destruction of lung architecture, which leads to the infection of regional endothelial cells and produces a hypoxic environment that further stimulates PAI-1 production.
33038618 Coagulopathy and vascular endothelial dysfunction have been proposed as the complications of COVID-19 which can ultimately lead to ischemic stroke.
33040020 COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF).
33042157 Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.
33043287 Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection is associated with hypercoagulability caused by direct invasion of endothelial cells andproinflammatory cytokine release.
33045255 Acute tubular injury (n=14), collapsing glomerulopathy (n=7) and endothelial injury/thrombotic microangiopathy (n=6) were the most common histologic findings. […] While acute tubular injury was seen among the majority of them, uncommon pathology such as collapsing glomerulopathy and acute endothelial injury were detected, and most of these patients progressed to irreversible kidney injury and dialysis.
33045281 Concentrations of inflammatory and endothelial dysfunction biomarkers were determined at clinical presentation.
33045354 Unlike other SARS viruses, SARS-CoV2 does not solely impact the respiratory system, but additionally leads to inflammation of endothelial cells, microvascular injuries and coagulopathies, thereby affecting multiple organs.
33046353 Among its manifestations, it can develop a thrombotic disease, both venous and arterial, due to excessive inflammation that affects the vascular system, with platelet activation and endothelial dysfunction, among other mechanisms.
33049279 The primary target of the SARS-CoV-2 virus is the human lungs governed by the ACE-2 receptor of epithelial type II cells/endothelial cells, which promote modulation of the immune response of host cells through generating cytokine storm, inflammation, severe pneumonia symptoms, and secondary complications such as acute respiratory distress syndrome. […] MSCs have shown to combat the disease via various pathways such as repairing the lung epithelial and endothelial cells, reducing hyperimmune response, maintaining the renin-angiotensin system.
33049751 Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype.
33050220 All theseresponses may induce endothelial dysfunction, myocardial injury, plaque instability, and AMI.Disease severity and mortality are increased by cardiovascular comorbidities.
33051389 A proposed underlying mechanism is that SARS-CoV-2 infects vascular endothelial cells via the angiotensin-converting enzyme 2 (ACE2) and causes inflammation.
33052496 The HHT pathogenic angiogenesis and endothelial injury in COVID-19 are discussed using data from RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry. […] The endothelial damage and the consequent angiogenic process in COVID-19 patients deserve further investigation.
33053430 Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. […] Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. […] Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.
33054759 In this review, we summarize the literature regarding the effects of mechanical stress on the fundamental cells constituting the alveoli in the process of pulmonary fibrosis, particularly on epithelial cells, capillary endothelial cells, fibroblasts, mast cells, macrophages and stem cells.
33058027 Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay. . […] Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. […] PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality. […] Our data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19.
33058948 Microvascular complement deposition strongly colocalized in situ with the SARS-CoV-2 viral proteins including spike glycoproteins in the endothelial cells as well as the viral receptor ACE2 in lesional and nonlesional skin; viral RNA was not evident. […] Although the samples from severely ill patients with COVID-19 were from grossly normal skin, light microscopically focal microvascular abnormalities were evident that included endothelial cell denudement, basement membrane zone reduplication, and small thrombi. […] It is concluded that complement activation is common in grossly normal skin, especially in the subcutaneous fat which may provide a link between severe disease and obesity, in people with severe COVID-19, and the strong colocalization with the ACE2 receptor and viral capsid proteins without viral RNA suggests that circulating viral proteins (ie, pseudovirions) may dock onto the endothelial of these microvessels and induce complement activation.
33059757 MSC’s therapeutic effect is displayed in their ability to reduce the cytokine storm, enhance alveolar fluid clearance, and promote epithelial and endothelial recovery; however, the safest and most effective route of MSC delivery remains unclear.
33062077 However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.
33063256 In addition to the primary lung injury, many patients especially the ones with moderate to severe COVID-19 display evidence of endothelial damage, complement activation, which leads to a pro-coagulable state.
33065030 In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2.
33066908 One patient was treated with anakinra, an interleukin-1 inhibitor that may disrupt endothelial function. […] One patient was treated with tocilizumab, an interleukin-6 inhibitor that may have effects on endothelial function. […] Risk factors for posterior reversible encephalopathy syndrome in patients with coronavirus disease 2019 may include underlying infection or immunomodulatory agents with endothelial effects in conjunction with modest blood pressure fluctuations.
33067719 In the current study, we elucidated the effect of ET on the hCMEC/D3 human brain endothelial cell line. […] Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. […] 7KC induces a dose-dependent loss of cell viability and an increase in apoptosis and necrosis in the endothelial cells. […] This shows that ET needs to enter the endothelial cells to have a protective effect and is unlikely to act via extracellular neutralizing of 7KC. […] The protective effect on inflammation in brain endothelial cells suggests that ET might be useful as a nutraceutical for the prevention or management of neurovascular diseases, such as stroke and vascular dementia.
33068723 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to multi-system dysfunction with emerging evidence suggesting that SARS-CoV-2-mediated endothelial injury is an important effector of the virus.
33070537 Great attention has been paid to endothelial dysfunction (ED) in coronavirus disease 2019 (COVID-19). […] There is growing evidence to suggest that the angiotensin converting enzyme 2 receptor (ACE2 receptor) is expressed on endothelial cells (ECs) in the lung, heart, kidney, and intestine, particularly in systemic vessels (small and large arteries, veins, venules, and capillaries). […] As a result of endothelial activation and ED, the levels of pro-inflammatory cytokines (interleukin -1, interleukin-6 (IL-6), and tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1), von Willebrand factor (vWF) antigen, vWF activity, and factor VIII are elevated.
33070539 In this review we describe the rationale of the putative role of endothelial dysfunction in this event. […] Herein, we will briefly review (1) anti-inflammatory and anti-thrombotic effects of vitamin D, (2) vitamin D receptor and vitamin D receptor ligand, (3) protective role of vitamin D against endothelial dysfunction, (4) risk of vitamin D deficiency, (5) vitamin D deficiency in association with endothelial dysfunction, (6) the characteristics of vitamin D relevant to COVID-19, (7) the role of vitamin D on innate and adaptive response, (8) biomarkers of endothelial cell activation contributing to cytokine storm, and (9) the bidirectional relationship between inflammation and homeostasis. […] Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α. […] A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.
33073058 We argue that SARS-CoV-2 could have triggered the hemolytic process, which led to retinal hemorrhages due to endothelial anoxia from the low oxygen carrying capacity.
33074732 Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis.
33077917 Insights into the pathogenic mechanisms underlying SARS-CoV-2 infection and COVID-19 progression are emerging and highlight the critical role of the immunological hyper-response - characterized by widespread endothelial damage, complement-induced blood clotting and systemic microangiopathy - in disease exacerbation.
33078484 Dysfunctional microvascular support by pericytes or endothelial cells may increase the propensity for AF via increased myocardial inflammation, fibrosis, increased tissue edema, and interstitial hydrostatic pressure.
33081458 Their development is associated with hypercoagulation and endothelial dysfunction.
33081905 Sustained high levels of cytokines cause diffuse damage to pulmonary capillary endothelial cells and alveolar epithelial cells, resulting in acute respiratory distress syndrome (ARDS).
33081917 In addition, COVID-19 causes an endothelial disease following endotheliitis after the direct invasion of endothelial cells and a prothrombotic state secondary to the strong inflammatory response to infection.
33082714 Direct endothelial injury by viruses and dysregulation of clotting mechanisms due to cytokine storm are the major precipitating factors of mortality in COVID-19; both are attributed to a fundamental dysregulation of the immune system.
33082858 We used AutoDock vina and PyMOL software for molecular docking. )-vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a “drug-ingredient-target-pathway” effector network.
33086867 Given the central role of endothelial function in cardiovascular health, we herein provide a number of considerations that warrant future research and considering a paradigm shift toward identifying the molecular underpinnings of endothelial resilience.
33088822 The effects of COVID-19 are caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is the underlying actions of SARs-CoV-2 virions on the endothelial glycocalyx that we consider here. […] The endothelial glycocalyx layer is essential in maintaining normal fluid homeostasis, but is fragile and prone to pathophysiological damage. […] We therefore conclude that albumin binding to SARS-CoV-2 virions may inhibit the formation of the endothelial glycocalyx by inhibition of albumin transport binding sites.
33092737 Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019.
33093131 This may be the result of COVID-19-related endothelial injury, cytokine storm, or thrombotic microangiopathy.
33093981 COVID-19 is known to be characterized by coagulation activation and endothelial dysfunction, causing ischemic and hemorrhagic vascular syndromes. […] The angiotensin-converting enzyme (ACE) II receptor is expressed in circumventricular organs and in cerebrovascular endothelial cells, which play a role in vascular autoregulation and cerebral blood flow.
33094291 The present study investigates the effects of the heat shock protein 90 inhibitor Luminespib (AUY-922) towards the Kifunensine-triggered lung endothelial dysfunction. […] Our results indicate that the UPR inducer Luminespib counteracts the effects of Kifunensine in both human and bovine lung endothelial cells.
33096114 The presence of these inflammatory mediators in the vascular compartment leads to the activation of vascular endothelial cells platelets and neutrophils and the subsequent formation of platelet neutrophil complexes. […] These complexes in concert with activated endothelial cells interact to create a state of immunothrombosis.
33097419 We hypothesize that ischemic events are usually the result of the combined process of a pro-inflammatory and pro-coagulant state plus vascular endothelial dysfunction probably potentiated by hypoxia, hemodynamic instability, and immobilization, as reported in other cases.
33101215 Disruption of epithelial and endothelial barriers is a key clinical turning point that differentiates patients who are likely to develop severe COVID-19 outcomes: it marks a significant escalation in respiratory symptoms, loss of viral containment and a progression toward multi-organ dysfunction.
33102991 Endothelial damage and increased coagulation activity have been reported in some patients with COVID-19, resulting in a variety of thrombotic events.
33112891 Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells.
33114061 The discussed data showed a strict relationship among the inflammatory processes, diffuse alveolar, and endothelial damage.
33116032 Plasma levels of VWF antigen were extremely high, probably due to endothelial cell damage caused by COVID-19.
33117528 Severe acute respiratory syndrome coronavirus 2 causes severe pneumonia and endothelial injury that leads to a prothrombotic state that may be complicated by macrovascular and microvascular thrombosis. […] Complement activation is thought to contribute to endothelial injury and there are at least seven ongoing clinical trials testing six different anti-complement strategies for coronavirus disease 2019 (COVID-19), including eculizumab. […] Although eculizumab was unable to prevent the development of severe endothelial cell injury, as assessed by increasing D-dimer levels from 292 to 10 586 ng/mL, the patient eventually recovered following dexamethasone and convalescent plasma administration.
33118741 It has been reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces endothelial inflammation, therefore facilitating the progression of endothelial and vascular dysfunction in coronavirus disease 2019 (COVID-19) patients. […] Unfortunately, graft patency of the SV is low due to endothelial dysfunction and inflammation. […] We propose that SARS-CoV-2 might cause vascular inflammation, endothelial dysfunction, and thrombosis in coronary artery bypass graft vessels by binding angiotensin-converting enzyme 2 receptor. […] Moreover, we discuss the technique of SV graft harvesting and the therapeutic potential of focusing on endothelial dysfunction, vascular inflammation, and thrombosis for protecting coronary artery bypass grafts in COVID-19 infected CABG patients.
33120643 Descemet’s Membrane Endothelial Keratoplasty (DMEK) was done with the stripped donor DM in a patient with Fuch’s endothelial dystroph (FECD).
33121429 Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction.
33122241 Our findings support the notion that non-immune abnormalities such as hyperinflammation following cytokine storms and microvascular disorders due to vascular endothelial damage may lead to neurological symptoms in patients with SARS-CoV-2 infection.
33122620 These hematologic abnormalities are suspected to occur in the context of underlying immune dysregulation and endothelial dysfunction.
33123031 This likely leads to microcirculatory derangement with endothelial damage, profound inflammation, and coagulopathy that characterize the more severe clinical manifestations of COVID-19 infection.
33123154 Reports suggest a role of endothelial dysfunction and loss of endothelial barrier function in COVID-19. […] It is well established that the endothelial glycocalyx-degrading enzyme heparanase contributes to vascular leakage and inflammation.
33123364 Our findings suggest that activation of complement plays a role in the pathogenesis of COVID-19, leading to endothelial injury and lung damage.
33124029 In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction.
33124044 There are also some clues about the importance of endothelial and pericyte dysfunction and neuroinflammation in COVID-19 infection, related to complications and survival of the patients.
33124941 These responses result in increased signaling by thrombin (proteinase-activated) and purinergic receptors, which promote platelet activation and exert pathological effects on other cell types (e.g., endothelial cells, epithelial cells, fibroblasts), further enhancing inflammation and injury.
33134226 Researchers believe that smoking might increase the severity of infections caused by SARS-CoV-2 by altering the viability and integrity of the BBB, while promoting the expression of ACE2 in endothelial cells, glia, and neurons.
33139116 To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients. […] Markers of complement activation (SC5b-9 and C5a) and endothelial perturbation (von Willebrand factor [vWF], tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1], soluble thrombomodulin [sTM], and soluble endothelial selectin [sE-selectin]) were measured in plasma. […] The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy.
33140037 Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents have become the most prevalent intraocular procedure as they represent the major therapeutic modality for prevalent retinal conditions such as age-related macular degeneration (AMD) and diabetic retinopathy.
33142828 Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity.
33142844 The telltale signs of perpetual on-going coagulation and fibrinolytic cascades underscore the presence of diffuse endothelial damage in the patients with COVID-19. […] These mechanisms are triggered by widespread endothelial cell damage (endotheliopathy), the dominant driver of macro- and micro-vascular thrombosis in these patients.
33142989 We propose a paradigm for the two-site attack of SARS-CoV-2 leading to ENaC hyperactivation and inactivation of the ACE2 complex, which collapses cell osmolality and leads to rupture and/or necrotic death of swollen pulmonary, endothelial, and cardiac cells, thrombosis in infected and non-infected tissues, and aberrant sensory and neurological perception in COVID-19 patients.
33143053 Since we and others have shown that endothelial cells play a pivotal role in the pathogenesis of the coronavirus disease 2019 (COVID-19), we mechanistically validated miR-98-5p as a regulator of TMPRSS2 transcription in two different human endothelial cell types, derived from the lung and from the umbilical vein.
33155525 The article describes the cellular immunology (macrophages, T cells, B cells, dendritic cells, NK cells and pulmonary epithelial cells (PEC) and vascular endothelial cells) and the associated immune response during COVID-19.
33156022 Major histopathologic findings were lymphocytic eccrine inflammation and a spectrum of vasculopathic findings to include superficial and deep angiocentric-perivascular lymphocytic inflammation, lymphocytes in vessel walls (lymphocytic vasculitis), endothelial swelling, red blood cell extravasation, and focal deposits of fibrin in both vessel lumina, and vessel walls.
33157320 The damage endothelial system provides a good explanation for the various complications seen in COVID-19 patients. […] These observations lead us to suspect that endothelial cells are a barrier that must be breached before progression to severe disease. […] Endothelial intracellular defences are largely dependent of the activation of the interferon (IFN) system. […] Additionally, the increased risk of death with diseases that have underlying endothelial dysfunction suggest that endothelial NOS-derived nitric oxide could be the main defence mechanism.
33158808 Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. […] COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia.
33161318 A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury. […] This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications. […] Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure. […] Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19. […] Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation. […] Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events. […] Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction. […] Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients. […] Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19.
33161843 The mechanisms underlying cerebral endothelial susceptibility and response to SARS-CoV-2 are unknown yet critical to understanding the association of SARS-CoV-2 infection with cerebrovascular events. […] Endothelial cells were isolated from human brain and analyzed by RNA sequencing. […] Human umbilical vein and human brain microvascular cells were used in both monolayer culture and endothelialized within a 3-dimensional printed vascular model of the middle cerebral artery. […] Recombinant SARS-CoV-2 S protein and S protein-containing liposomes were used to measure endothelial binding by immunocytochemistry. gene expression and protein levels were progressively increased by vessel size and flow rates. […] SARS-CoV-2 S protein-containing liposomes were detected in human umbilical vein endothelial cells and human brain microvascular endothelial cells in 3-dimensional middle cerebral artery models but not in monolayer culture consistent with flow dependency of ACE2 expression. […] Binding of SARS-CoV-2 S protein triggered 83 unique genes in human brain endothelial cells including upregulation of complement component C3. […] Brain endothelial cells are susceptible to direct SARS-CoV-2 infection through flow-dependent expression of ACE2.
33172748 COVID-19 can cause cardiovascular complications or deterioration of coexisting CVD through direct or indirect mechanisms, including viral toxicity, dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial cell damage and thromboinflammation, cytokine storm, and oxygen supply-demand mismatch.
33173491 The proposed mechanism being excessive inflammation, platelet activation, endothelial dysfunction, and stasis.
33174406 Moreover, the hyper-inflammation with endothelial dysfunction is likely be responsible of both pulmonary in-situ platelet aggregation and deep thrombosis potentially leading to severe pulmonary embolism and right ventricular failure.
33176009 The German physician Rudolph Virchow, about two centuries ago, described three pivotal factors contributing together to thromboembolic risk: endothelial injury, hypercoagulability, and blood stasis.
33177848 The receptors for pro-inflammatory cytokines, especially IL6ST, were notably concentrated in endothelial cells, macrophages, spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging autoimmune mechanisms.
33179785 A strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cell growth was identified. […] Endothelial cell distortion generated vascular lumen obliteration and striking erythrocyte and serum extravasation. […] COVID-19 could comprise an obliterative microangiopathy consisting on endothelial and myointimal growth with complement activation.
33181144 It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. […] The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2.
33181158 Briefly, entry of the virus into microvessels can profoundly disrupt the local renin-angiotensin system, cause endothelial injury, activate the complement cascade and induce powerful thromboinflammatory reactions, involving, in particular, von Willebrand factor, that, if widespread, may lead to microvascular plugging, ischemia and, ultimately, organ failure.
33182802 These includes endothelial and coagulation dysfunction with disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS), along with the occurrence of neurological alterations.
33183974 The angiotensin-converting enzyme 2 (ACE2), which acts as the SARS-CoV-2 receptor, is present in endothelial cells and has been noted within the human placenta.
33189452 Currently, it is known that endothelial cell dysfunction is a critical event in the infection by this virus. […] However, in a representative percentage of patients with COVID-19, neither cardiovascular disease nor diabetes mellitus, which could be linked with endothelial dysfunction, has been reported. […] Previous evidence has shown the presence of early endothelial dysfunction in healthy subjects but with a family history of type 2 diabetes (FH-DM2), where glucose metabolism, the synthesis of nitric oxide (NO), reactive oxygen species (ROS), as well as expression of genes involved with their synthesis are impaired. […] Besides, in subjects with an FH-DM2, the presence of hyperinsulinemia and high glucose levels are common events that could favor the infection of endothelial cells by the coronavirus. […] Interestingly, both events have been reported in patients with COVID-19, in whom hyperinsulinemia increases the surface expression of ACE2 through a diminution of ADAMTS17 activity; whereas hyperglycemia induces higher expression of ACE2 in different tissues, including microvascular endothelial cells from the pancreatic islets, favoring chronic hyperglycemia and affecting the release of insulin. […] Therefore, we hypothesized that an FH-DM2 should be considered an important risk factor, since the individuals with this background develop an early endothelial dysfunction, which would increase the susceptibility and severity of infection and damage to the endothelium, in the patient infected with the SARS-CoV-2.
33189832 Once induced by hypoxia, the Warburg effect becomes active in lung endothelial cells, particularly in the presence of atherosclerosis, thereby promoting vasoconstriction and micro thrombosis. […] Understanding the role of the Warburg effect in COVID-19 can be essential to developing molecules reducing infectivity, arresting endothelial cells activation and the pro-inflammatory cascade.
33190109 It is postulated that either the cytokine storm induced by the viral infection or endothelial damage caused by viral binding to the ACE-2 receptor may activate a cascade leading to a hypercoaguable state.
33190387 Intense endothelial immunoreactivity pattern for fractalkine expression was observed.
33191474 COVID-19-induced HF is manifested via different mechanisms, including, but not limited to, (1) virus-induced infiltration of inflammatory cells, which could impair the function of the heart; (2) pro-inflammatory cytokines (monocyte chemoattractant protein-1, interleukin-1β; interleukin-6; tumor necrosis factor-α) that could cause necrosis and death of the myocardium; (3) endothelial injury coupled with micro-thrombosis which could damage the endocardium; and (4) acute respiratory distress syndrome and respiratory failure that could lead to heart failure due to severe hypoxia.
33195371 As a result, these unhealthy behaviors are typically linked to vascular endothelium damage (endothelial dysfunction), which is a first step for the development of cardiovascular disease (CVD). […] Given that CVD is the main cause of morbidity and mortality worldwide, attenuating the progression of endothelial dysfunction is very important for the control of CVD. […] Consuming vegetable rich in nitrate, such as beetroots, may be an effective way to prevent endothelial dysfunction. […] Several emerging studies have recommended beetroot juice in order to improve endothelial function in hypertensive, hypercholesterolemic individuals, as well as in those with CVD risk factors.
33195477 Diseased small vessels in PAH show decreased lumens, thicker walls, endothelial dysfunction, and oxidative stress and inflammation.
33195487 Activation of endothelial cells via the immune-mediated inflammatory response and viral infection of either endothelial cells or cells involved in endothelial homeostasis, are some of the multifaceted mechanisms potentially involved in the pathogenesis of vascular dysfunction within COVID-19 patients. […] In this review, we examine the evidence of vascular manifestations of SARS-CoV-2, the potential mechanism(s) of entry into vascular tissue and the contribution of endothelial cell dysfunction and cellular crosstalk in this vascular tropism of SARS-CoV-2.
33196292 Coronavirus disease 2019 (COVID-19) is associated with derangement in biomarkers of coagulation and endothelial function and has been likened to the coagulopathy of sepsis.
33200786 It will be shown that increased PSS has potential in vivo to exert anti-viral properties of NO as well as to benefit endothelial manifestations of COVID-19 thereby serving as a safe and effective backstop.
33200824 The widespread endothelial damage due to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi-organs dysfunction. […] The aim of this study was to evaluate the role of Mid-regional proAdrenomedullin (MR-proADM) as a marker of SARS CoV2-related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality.
33205222 COVID-19 causes vascular endothelial injury, vasculitis and prothrombotic state which might be the underlying cause of hemorrhagic cutaneous manifestations, disseminated intravascular coagulation (DIC), and multiple organ failures.
33206631 Vascular endothelial growth factor could be the pathophysiological link between the 2 conditions.
33208052 Pre-existing endothelial dysfunction and an impaired innate immune response promote the development by the viral infection of an acute endothelialitis in the pulmonary microcirculation complicated by abnormal vasoconstrictor responses, luminal plugging by inflammatory cells, and intravascular thrombosis. […] This endothelialitis extends into the systemic circulation what may lead to acute myocardial injury, myocarditis, and thromboembolic complications both in the arterial and venous circulation.
33208493 This raises questions regarding whether microhaemorrhage occurs from endothelial dysfunction due the direct effect of SARS-CoV-2 infection or from the secondary effects of critical illness and hypoxia.
33208929 RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. […] Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.
33210709 The protective RAS has numerous beneficial actions, including anti-inflammatory, anti-coagulative, anti-fibrotic effects along with endothelial and neural protection; opposite to the deleterious effects caused by heightened stimulation of angiotensin AT1R. […] Given that patients with severe COVID-19 exhibit an excessive immune response, endothelial dysfunction, increased clotting, thromboses and stroke, enhancing the activity of the protective RAS is likely beneficial.
33211428 These coagulopathies likely result from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection-elicited systemic inflammation and endothelial damage.
33213181 To describe the effective use of only 50% air fill of the anterior chamber for rebubbling partially detached Descemet Membrane Endothelial Keratoplasty (DMEK) grafts at the slit lamp at a time of restricted operating theatre access during the COVID-19 pandemic.
33214651 In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19.
33217763 The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. […] This means that the blood-endothelial barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.
33219572 COVID-19 generates a complex systemic inflammatory response that can lead to death due to wide macrophage activation, endothelial damage, and coagulation in critically ill patients.
33221129 Magnesium deficiency primes phagocytes, enhances granulocyte oxidative burst, activates endothelial cells and increases the levels of cytokines, thus promoting inflammation.
33221483 The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2.
33222915 We believe this is related to the tropism of SARS-CoV-2 to the endothelial lining of the cerebral vasculature via their angiotensin-converting enzyme (ACE) II receptors.
33224380 Enhanced ACE2 expression, pre-existing endothelial dysfunction and procoagulant state induced by adipocytokines dysregulation in metabolic syndrome may play a crucial role for the development of severe COVID-19.
33224588 COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while having lung injury as its most prominent feature, has been increasingly shown to affect endothelial cell function and the microvasculature.
33225251 As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state.
33231313 This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID-19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes.
33232769 The treatment of human pulmonary artery smooth muscle cells or human pulmonary artery endothelial cells with recombinant SARS-CoV-2 spike protein S1 subunit (Val16 - Gln690) at 10 ng/ml (0.13 nM) caused an activation of MEK phosphorylation.
33233715 The pulmonary endothelium is a metabolically active continuous monolayer of squamous endothelial cells that internally lines blood vessels and mediates key processes involved in lung homoeostasis. […] Many of these processes are disrupted in acute respiratory distress syndrome (ARDS), which is marked among others by diffuse endothelial injury, intense activation of the coagulation system and increased capillary permeability. […] Endothelial cell damage has an important role in the pathogenesis of ARDS and several biomarkers of endothelial damage have been tested in determining prognosis. […] By further understanding the endothelial pathobiology, development of endothelial-specific therapeutics might arise. […] In this review, we will discuss the underlying pathology of endothelial dysfunction leading to ARDS and emerging therapies.
33239231 Seventh, AAT inhibition of endothelial cell apoptosis may limit the endothelial injury linked to severe COVID-19-associated acute lung injury, multi-organ dysfunction, and pre-eclampsia-like syndrome seen in gravid women.
33239293 While restoration of microcapillaries is critical to avoid mortality, therapeutic targeting of this process requires a greater understanding of endothelial repair mechanisms. […] Ablation of chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF2) (Nr2f2), a transcription factor implicated in developmental angiogenesis, reduced endothelial proliferation, exacerbating viral lung injury in vivo. […] Upon influenza injury, nuclear factor κB suppresses COUP-TF2, but surviving endothelial cells ultimately reestablish vascular homeostasis dependent on restoration of COUP-TF2.
33240326 The analysis of the KEGG’s pathways showed modulation of several gene networks related to the leucocyte transendothelial migration, cytoskeleton and adhesion system. […] The analysis of the modulated genes gave evidence for the involvement of PM in the endothelial disease, coagulation disorders, diabetes and reproductive toxicity, supporting the hypothesis that PM, directly or through molecular interplay, affects the same molecular targets as so far known for SARS-COV-2, contributing to the cytokines storm and to the aggravation of the symptoms triggered by COVID-19.
33245005 The SARS-CoV-2 infection triggers inflammation via the JAK/STAT pathway leading to recruitment of pneumocytes, endothelial cells, macrophages, monocytes, lymphocytes, natural killer cells and dendritic cells progressing towards cytokine storm.
33246294 Histopathologically, this condition is known as diffuse alveolar damage which consists of permanent damage to the alveoli epithelial cells and capillary endothelial cells, with consequent hyaline membrane formation and eventually intracapillary thrombosis.
33246355 Our in silico studies revealed that one SNP in the vascular endothelial growth factor receptor 2 (VEGFR2) gene was predicted as deleterious using sorting intolerant from tolerant.
33248385 There were three key findings: 1) high copy infectious virus was limited mostly to the alveolar macrophages and endothelial cells of the septal capillaries; 2) viral spike protein without viral RNA localized to ACE2+ endothelial cells in microvessels that were most abundant in the subcutaneous fat and brain; 3) although both infectious virus and docked viral spike protein was associated with complement activation, only the endocytosed pseudovirions induced a marked up-regulation of the key COVID-19 associated proteins IL6, TNF alpha, IL1 beta, p38, IL8, and caspase 3. […] Importantly, this microvasculitis was associated with characteristic findings on hematoxylin and eosin examination that included endothelial degeneration and resultant basement membrane zone disruption and reduplication. […] It is concluded that serious COVID-19 infection has two distinct mechanisms: 1) a microangiopathy of pulmonary capillaries associated with a high infectious viral load where endothelial cell death releases pseudovirions into the circulation, and 2) the pseudovirions dock on ACE2+ endothelial cells most prevalent in the skin/subcutaneous fat and brain that activates the complement pathway/coagulation cascade resulting in a systemic procoagulant state as well as the expression of cytokines that produce the cytokine storm. […] The data predicts a favorable response to therapies based on either removal of circulating viral proteins and/or blunting of the endothelial-induced response.
33249060 Consistent with known DHODH requirements for immunomodulatory cytokine production, PTC299 inhibited the production of interleukin (IL)-6, IL-17A (also called IL-17), IL-17 F, and vascular endothelial growth factor (VEGF) in tissue culture models.
33249290 Endothelial cells express surface angiotensin-converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that promotes the infection of endothelial cells showing activation and damage.
33249452 It suggests that cortisol-associated activation of the Mineralocorticoid Receptor (MR) in epithelial and endothelial cells infected with the virus stimulates the release of ATP which then acts back on purinergic receptors. […] In endothelial cells it could stimulate exocytosis of Weibel-Palade (WP) bodies that contain angiopoietin-2 which is important in the pathogenesis of the Acute Respiratory Distress Syndrome (ARDS) by increasing capillary permeability and Von Willebrand Factor which mediates platelet adhesion to the endothelium and hence clotting.
33254192 Vascular endothelial damage, added to the development of disseminated intravascular coagulation, affects the prognosis and mortality from this disease.
33254525 A recent study suggested that Covid-19 leads to a severe extrahepatic vitamin K insufficiency, which could lead to impaired activation of extrahepatic proteins like endothelial anticoagulant protein S in the presence of normal hepatic procoagulant activity.
33254535 Recent studies show that the endothelial dysfunction caused by the virus contributes to its high morbidity and mortality. […] An emerging technology is currently being tested to predict the cardiovascular risk via non-invasively measuring the endothelial dysfunction. […] This paper reviews how the assessment of endothelial dysfunction using this technology can be used as a potential parameter in the prognostication and management of COVID-19 patients.
33254538 This leads to overstimulation of the classic pathway with adverse cardiovascular and respiratory effects, hypercoagulation, endothelial dysfunction, inflammation and insulin resistance.
33254586 Cerebrovascular complications are the end result of multiple and complex pathophysiology mechanisms involving endothelial dysfunction and activation, development of chronic inflammatory cascades leading to a prothrombotic state in addition to cardioembolic stroke due to cardiomyopathy and arrhythmias.
33256484 In particular, the pharmacological approach should be used in advanced phases characterized by clinical signs of vascular disease, whilst the nutraceutical approach may represent a promising preventive strategy to preserve the integrity of the endothelial tissue.
33257090 Herein, we review the latest evidence that shows that B12 deficiency associates in multiple areas very similar to where COVID-19 exerts its damaging effects: immunologically; microbiologically; haematologically; and through endothelial cell signalling-supporting the hypothesis that B12 deficiency is a potential modifiable risk factor in our fight against COVID-19.
33257876 SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings.
33262177 The former include: (1) age-related increase in endothelial damage and changes in clotting function; (2) higher density, increased affinity and different distribution of angiotensin converting enzyme 2 receptors and transmembrane serine protease 2; (3) pre-existing coronavirus antibodies (including antibody-dependent enhancement) and T cells; (4) immunosenescence and inflammaging, including the effects of chronic cytomegalovirus infection; (5) a higher prevalence of comorbidities associated with severe COVID-19 and (6) lower levels of vitamin D.
33267662 Levels of the NET markers also correlated with white blood cells, neutrophils, inflammatory cytokines, and C-reactive protein, as well as to markers of in vivo coagulation, fibrinolysis, and endothelial damage.
33272285 Most critically ill Covid-19 patients succumb to multiple organ failure and/or sudden cardiac arrest (SCA) as a result of comorbid endothelial dysfunction disorders which had probably aggravated by conventional mechanical assist devices. […] Even worse, mechanical ventilators prevent the respiratory pump from performing its crucial function as a potential generator of endothelial shear stress (ESS) which controls microcirculation and hemodynamics since birth.
33278121 These emerging therapeutics can modulate the immune response, reduce epithelial injury, target endothelial and vascular dysfunction, have anticoagulant effects, and enhance ARDS resolution.
33279630 These included the development of hyaline membranes, thrombi, endothelial inflammation, haemorrhages and angiogenesis.
33281125 The possible mechanisms of cardiovascular injury are endothelial dysfunction, diffuse microangiopathy with thrombosis and increased angiotensin II levels.
33281415 Evidence of inflammatory-mediated thrombosis and endothelial injury are possible explanations which would support the use of immunotherapy in addition to anticoagulation for treatment or prevention of thromboembolic events.
33282075 Available data indicate that COVID-19 and cardiovascular disease share pathomechanisms and risk factors which include ACE2 receptor invasion and renin-angiotensin system signaling, oxidative stress, systemic inflammation, and endothelial dysfunction.
33282193 Using plasma profiling of patients with COVID-19, we identified circulating markers that segregated with disease severity: markers of angiogenesis (VEGF-A, PDGF-AA and PDGF-AB/BB) were elevated in hospitalized patients with non-critical COVID-19 infection, while markers of endothelial injury (angiopoietin-2, FLT-3L, PAI-1) were elevated in patients with critical COVID-19 infection. […] In survival analysis, elevated markers of endothelial injury (angiopoietin-2, follistatin, PAI-1) were strongly predictive of in-hospital mortality. […] Our findings demonstrate that non-critical and critical phases of COVID-19 disease may be driven by distinct mechanisms involving key aspects of endothelial cell function, and identify drivers of COVID-19 pathogenesis and potential targets for future therapies.
33282201 Pulmonary arterial hypertension (PAH) and novel coronavirus (SARS-CoV-2) disease COVID-19 are characterized by extensive endothelial dysfunction and inflammation leading to vascular remodeling and severe microthrombi and microvascular obliterative disease.
33282314 COVID-19 can be associated with multiple organ failure due to vascular endothelial injury.
33282586 In patients with SARS-CoV1-, SARS-CoV2-, and the Middle East respiratory syndrome coronavirus (MERS-CoV)-mediated hypercoagulability, the risk of thrombosis appears to be multifactorial - direct viral cytopathological effects, a pro-inflammatory state, cytokine storm, hypoxia-inducible thrombosis, and endothelial inflammation culminating in the formation of intra-alveolar or systemic fibrin clots.
33284859 Introduction of culture supernatant from SARS-CoV-2 spike expressing cells on a model human liver endothelial Cell line (TMNK-1), where transmembrane IL-6R is poorly expressed, resulted in the induction of STAT3 Tyr705 phosphorylation as well as MCP-1 expression.
33290544 Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.
33291346 The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. […] Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. […] In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. […] The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. […] In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. […] Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.
33291622 Histology demonstrated perivascular and periadnexal lymphohistiocytic infiltrates and endothelial dominated MxA-staining, as well as pJAK1 activation.
33293527 While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. […] Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system.
33295423 Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay.
33296106 Recent articles report elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased COVID-19 patients.
33300152 In this review, we comprehensively examine current evidence of SARS-CoV-2 infection in various neural cells including neurons, microglia/macrophages, astrocytes, pericytes/endothelial cells, ependymocytes/choroid epithelial cells, and neural stem/progenitor cells.
33301441 Retinoic acid (RA) has been shown to improve epithelial and endothelial barrier function and development and even suppress damage inflicted by inflammation on these barriers through regulating immune cell activity.
33302737 SARS-CoV-2 leads to the production of proinflammatory cytokines, causing immune-mediated tissue damage, disruption of the endothelial barrier, and uncontrolled thrombogenesis.
33306138 COVID-19 affects not only the epithelial cells of the lung parenchyma via ACE2, but also endothelial cells across the whole body thus leading to generalized endothelial damage and inflammation, so-called endotheliitis. […] The histological morphology of endotheliitis comprises the accumulation of lymphocytes, plasma cells and macrophages beneath the endothelial cells and within the perivascular spaces. […] Endothelial cells play an important role in the regulation of vascular tone and the maintenance of vascular homeostasis. […] Patients with pre-existing endothelial dysfunction (male sex, smoking, hypertension, diabetes, obesity, and established cardiovascular disease) are particularly vulnerable and have adverse outcomes in COVID-19.
33307996 Here, we review the recent literature and discuss the possible association of SARS-CoV-2-mediated endothelial injury and cardiovascular disorders with cerebrovascular complications.
33308935 Furthermore, SarsCov2 creates Reactive Oxygen Species (ROS), which are toxic and generate endothelial dysfunction.
33310152 Senior individuals are more susceptible to the irreversible outcomes of endothelial barrier dysfunction, the hallmark of Acute Respiratory Distress Syndrome (ARDS). […] Endothelial hyperpermeability has been associated with both the progression and establishment of the COVID-19 - related respiratory failure. […] In the present study we investigated the in vitro effects of Metformin in the permeability of bovine pulmonary artery endothelial cells. […] Our preliminary results suggest that moderate doses (0.1, 0.5, 1.0 mM) of this anti-diabetic agent enhance the vascular barrier integrity, since it produces an increase in the transendothelial resistance of endothelial monolayers.
  1. Activation of the coagulation factor XII on the surface of SARS-CoV-2 infected endothelial cells may trigger the prekallikrein/kallikrein/kinin system producing bradykinin. […] 2) The endothelial system is dysregulated in elderly patients, resulting in potentially higher factor XII activities on the surface of damaged endothelial cells in the stiffened arteries.
33312255 Despite the evident difference in tropism, both conditions develop with severe endothelial dysfunction, microangiopathy and important inflammatory response, responsible for MODS.
33312949 The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs).
33316234 Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation, and inflammatory reaction, leading to acute respiratory failure and multi-organ dysfunction.
33317616 Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia).
33321496 Derangements in the innate and adaptive immune systems may be responsible for a reduced antiviral response, whereas chronic activation of the innate immune system and endothelial dysfunction provide a background for a more severe course.
33325084 Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor.
33326604 Endothelial cell (EC) activation plays a key role in the pathogenesis of pulmonary microvascular occlusion, which is a hallmark of severe coronavirus disease 2019 (COVID-19).
33326977 When viruses invade the glomeruli from the bloodstream, glomerular endothelial cells (GECs) initiate the innate immune reactions.
33329052 The role of hemodynamic changes in hypertension that might aggravate myocardial injury in the setting of COVID-19, including endothelial dysfunction, arterial stiffness, and left ventricle hypertrophy, are also discussed.
33329934 Direct viral toxicity, pro-inflammatory and pro-thrombotic induction, endothelial damage, immune imbalance, and dysregulation of the renin-angiotensin-aldosterone system are the mechanisms underlying the viral potential of multiple organ damage.
33330852 Recent evidence suggests that this mechanism affects the vascular barrier function, by modulating lung endothelial permeability.
33333472 Considering their antioxidative, anti-arrhythmic, antithrombotic properties and their beneficial effect on endothelial dysfunction, along with the increased risk of mortality of patients at high cardiovascular risk infected by SARS-CoV-2, statins and PCSK9 inhibitors might prove effective against the cardiovascular and thromboembolic complications of COVID-19.
33334050 Mounting recent evidence supports the involvement of cardiovascular complications and endothelial dysfunction in COVID-19 syndrome, in addition to respiratory disease.
33334590 Moderate-severe disease is associated with a high incidence of pulmonary embolisms, generally peripherally distributed and associated with endothelial damage, prolonged stays in bed, and coagulopathy.
33336781 PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm.
33343584 During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. […] Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19.
33348007 The elimination of this enzyme by the viral spike protein results in excessive activation of phagocytes, migration into the tissues via the high endothelial venules, and an oxidative burst.
33348719 Myocardial and endothelial expression of ACE2 could account for the growing body of reported evidence of myocardial injury in severe forms of Human Coronavirus Disease 2019 (COVID-19).
33349213 H2 is compared with established treatments such as targeted temperature management, and we discuss its possible mechanisms of action, including the recently identified suppression of TNF-α-mediated endothelial glycocalyx degradation by inhaled H2 .
33352699 Vascular endothelial dysfunction has been suggested as a common feature of high-risk patients prone to severe COVID-19, and measurement of vascular endothelial function may be recommended for predicting severe conditions in high-risk patients with COVID-19. […] However, fragmented vascular endothelial glycocalyx (VEGLX) is elevated in COVID-19 patients, suggesting that it may be useful as a prognostic indicator.
33354650 Severe novel corona virus disease 2019 (COVID-19) infection is associated with a considerable activation of coagulation pathways, endothelial damage, and subsequent thrombotic microvascular injuries.
33357215 In addition, the damage to endothelial cells after viral infection and/or activation of endothelium by pro-inflammatory cytokines, such as IL-1β, IL-6, IFN-γ, IL-8, and TNF-α induces platelets and monocyte aggregation in the vascular wall and expression of tissue factor (TF). […] The PtdSer exposure may be an important mechanism related to ADAM17-mediated ACE2, TNF-α, EGFR and IL-6R shedding, and the activation of TF on the surface of infected endothelial cells.
33360731 Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. […] It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. […] Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.
33361764 Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation. […] Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier, promoting pro-coagulative state, inducing endothelial inflammation, and even mediating leukocyte infiltration. […] This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.
33362713 The central and peripheral protective actions exerted following melanocortin receptor activation could allow dampening the harmful events that trigger the cytokine storm and endothelial dysfunction while sustaining the beneficial signals required to elicit repair mechanisms.
33368021 In addition, there seem to be features of a strong local pulmonary thrombotic microangiopathy and direct endothelial cell infection and injury by the virus that affect the coagulopathic response to severe COVID-19.
33369698 Osteopontin (OPN) is a glycoprotein expressed in various cell types, such as bone, immune, smooth muscle, epithelial and endothelial cells.
33372179 Instead, ACE2 was detected in airway Club cells and endothelial cells at birth, and then AT2 cells at one year of age.
33375371 Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. […] In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. […] We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. […] Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. […] Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.
33378321 Endothelial injury and augmented innate immune response are implicated in the development of diffuse macro- and microvascular thrombosis in COVID-19.
33380117 However, in some patients, COVID-19 infection can be severe, with hypercoagulation being a common finding, with vascular endothelial damage and the consequent risk of venous and arterial thrombotic complications.
33380345 Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. […] Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. […] It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted.
33382919 Autopsy studies have confirmed thrombotic disease not only at the macrovascular scale (pulmonary emboli, venous thromboses) but also with microthrombi in alveolar capillaries and severe endothelial injury.
33386559 Disordered coagulation, endothelial dysfunction, dehydration and immobility contribute to a substantially elevated risk of deep venous thrombosis, pulmonary embolism (PE) and systemic thrombosis in coronavirus disease 2019 (Covid-19).
33388022 Other factors contributing to a more severe course of COVID-19 include the co-existence of obesity in T2DM; the endothelial inflammation induced by the SARS-CoV-2 infection, which aggravates the endothelial dysfunction observed in both T1DM and T2DM; and the hypercoagulability presented in COVID-19 infection that increases the thrombotic tendency in DM.
33390561 The expression of this receptor in endothelial cells of blood-brain barrier (BBB) shows that SRAS-CoV-2 may have higher neuroinvasive potential compared to known coronaviruses.
33391014 SARS-CoV-2 damages endothelial cell and pneumocyte, resulting in hemostatic disorder and ARDS.
33392206 This includes the induction of vascular hyper-permeability and vasogenic edema by exRNA via the activation of the “vascular endothelial growth factor” (VEGF) receptor-2 system, as well as the recruitment of leukocytes to the inflamed endothelium, the M1-type polarization of inflammatory macrophages, or the role of exRNA as a pro-thrombotic cofactor to promote thrombosis.
33395482 Recent findings indicated that SARS-CoV-2 related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms.
33396592 Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families.
33401632 The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia.
33408195 Distinctive microvascular abnormalities in COVID-19 include endothelial inflammation, disruption of intercellular junctions and microthrombi formation. […] This state-of-the-art review will explore the pathobiological mechanisms of immunothrombosis and VTE in COVID-19 focusing on: COVID-19-associated coagulopathy, pathology, endothelial dysfunction and haemostasis, the immune system and thrombosis, genetic associations and additional thrombotic mechanisms.
33410706 Patients with severe coronavirus disease 2019 (COVID-19) may have endothelial inflammation, pseudoaneurysm, and an increasing risk of bleeding, especially during surgical procedures.
33411411 We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. […] Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. […] Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19.
33412365 The ECG abnormalities in COVID-19 may be due to cytokine storm, hypoxic injury, electrolyte abnormalities, plaque rupture, coronary spasm, microthrombi, or direct endothelial or myocardial injury.
33415422 Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis.
33419752 Individuals with HHT have been found to have abnormal plasma concentrations of transforming growth factor beta and vascular endothelial growth factor secondary to mutations in ENG, ACVRL1 and MADH4.
33421689 Taking into consideration the vital role of selenoproteins in maintaining an adequate immune response, endothelial homeostasis and a non-prothrombotic platelet activation status, we propose that impairment in selenocysteine synthesis, via perturbations in the aforementioned physiological functions, potentially constitutes a mechanism of coagulopathy in COVID 19 patients other than those developed in critical illness.
33421691 Herein, we provided the rationale for SARS-CoV-2 infection as endothelial dysfunction rather than respiratory disease. […] Accordingly, we strongly invited the researchers to look beyond pulmonary injury and shift their attention from respiratory disease to endothelial disorder.
33422689 While expressed on the surface of human cells, such as lung, heart, kidney, neurons, and endothelial cells (EC), ACE2 is the entry receptor for SARS-CoV-2.
33422990 SARS-CoV-2 targets epithelial and endothelial cells through the ACE2 receptor.
33423804 Dysregulated innate immune response in the lung due to viral-entry mediated angiotensin-I-converting enzyme 2 (ACE2) receptor downregulation causes endothelial injury in the pulmonary vasculature, inflammatory cytokine release, increased thrombin generation and impaired fibrinolysis.
33424598 This disease has been associated with inflammatory-induced homeostasis changes leading to endothelial dysfunction and a procoagulant state with multi-organ involvement, but the burden of thromboembolic complications in COVID-19 patients is currently unknown.
33425823 In this paradigm, the evidence supports the importance of endothelial injury and activation of the IL-1 pathway as a common determinant among MIS-C, Kawasaki disease, and Acute Rheumatic fever.
33436320 This condition can induce oxidative stress, decrease immune system function, impair endothelial function, induce apoptosis, and reduce antioxidant in the lungs.
33437350 Therefore, this review discusses the effects of pathophysiological mechanisms such as inflammatory storm, endothelial injury, phosphatidylserine expression, extracellular traps release on renal capillary thrombosis caused by COVID-19 infection.
33442282 Microvascular and endothelial cell injury, perivascular lymphocytic infiltrate, thrombosis, extremely dilated vessels and prominent deposits of C5b-9 were the main dermatologic pathological changes.
33443616 COVID-19 can also damage the endothelial system, causing microcirculatory disturbances and consequently leading to functional organ disorders. […] The combination of endothelial dysfunction with a generalized inflammatory state may contribute to the general pro-coagulative state described in patients with COVID-19 with increased risk of venous and arterial occlusions. […] The aim of this article is to describe the therapeutic utility of GCs in stabilizing the vascular endothelial barrier in COVID-19 infection. […] Indeed, we believe that the stabilization of the endothelial barrier and the anti-inflammatory effect of GCs could be the main effect underlying the therapeutic efficacy in COVID-19 patients.
33443926 Coronavirus pneumonia cases vs. non-novel coronavirus pneumonia controls showed marked VWF/FVIII elevation, suggesting specific virus-induced endothelial activation causing VWF/FVIII hypersecretion, which may represent a therapeutic target in novel coronavirus pneumonia.
33446327 Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells.
33448740 The rapid response to infection has been well defined and comprises a complex interaction of cytokine storm, endothelial dysfunction, inflammation, and pathologic coagulation.
33449299 To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. […] A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission. […] Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. […] Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality.
33449336 Nowadays, endothelial dysfunction, platelet activation, coagulation, and inflammatory host immune response are the subject of extensive researches in patients with COVID-19 disease.
33457379 This is a consequence of hypoxic vasoconstriction of the pulmonary circulation, the use of positive end-expiratory pressure (PEEP) in mechanical ventilation, pulmonary endothelial injury, and local inflammatory thrombotic and/or thromboembolic processes.
33464429 Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cell damage and thrombotic complications.
33469197 This review assesses markers of endothelial dysfunction (ED) associated with the maternal syndrome of preeclampsia (PE). […] In HIV infection, the trans-activator of transcription protein, which has homology with vascular endothelial growth factor, impairs angiogenesis, leading to endothelial injury and possible PE development despite neutralization of their opposing immune states. […] Despite the observed endothelial protective properties of DTG, there is a lack of evidence of its effects on pregnancy and COVID-19 therapeutics.
33470362 The neurological changes associated with COVID-19 have been frequently described, especially in cases of greater severity, and are related to multifactorial causes, such as endothelial dysfunction, inflammatory mediator release (cytokine storm), endothelial dysfunction and hypoxemia.
33472206 Results Ophthalmopathologically, eight eyes from four patients displayed swollen endothelial cells in congested choroidal vessels. […] In the eight eyes with evidence of changes due to SARS-CoV-2, immunohistochemical staining demonstrated fibrin microthrombi, apoptotic changes of endothelial and inflammatory cells. […] Discussion/Conclusion As already described in other organs of COVID-19 patients, the ophthalmological examination revealed-microthrombi, i.e. hypercoagulation and vasculopathy most probably due to endothelial damage. […] A possible viral spread to the endothelial cells via ACE-2 provides one pathophysiological explanation.
33472576 Microthrombosis is a prominent clinical feature of COVID-19, and 91.3% of dead patients had microthrombosis.Endothelial damage caused by SARS-CoV-2 cell invasion and subsequent host response disorders involving inflammation and coagulation pathways play a key role in the progression of severe COVID-19. […] Microvascular thrombosis may lead to microcirculation disorders and multiple organ failure lead to death.The characteristic pathological changes of DAD include alveolar epithelial and vascular endothelial injury, increased alveolar membrane permeability, large numbers of neutrophil infiltration, alveolar hyaline membrane formation, and hypoxemia and respiratory distress as the main clinical manifestations.
33477776 To determine whether endotheliopathy is involved in COVID-19-associated mortality, markers of endothelial damage were assessed in critically ill COVID-19 patients upon intensive care unit (ICU) admission. […] Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 and Ang-2, respectively), soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), soluble vascular endothelial (VE)-cadherin, and von Willebrand factor (vWf), were measured upon ICU admission. […] Hence, we conclude that in our cohort, ICU non-survivors had higher levels of specific endothelial markers compared to survivors.
33482680 The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. […] Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19).
33484708 Chloroquine causes zebroid deposits reminiscent of Fabry disease (α-galactosidase A deficiency) and endothelial cells are key targets of COVID-19. […] We have explored the effect of chloroquine on cultured endothelial cells and its modulation by recombinant α-galactosidase A (agalsidase). […] Following dose-response studies, 0.5 μg/mL chloroquine was added to cultured human endothelial cells. […] In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro test concentrations for COVID-19 therapy. […] These adverse effects of chloroquine on endothelial cell biology were decreased by agalsidase-β (P < 0.05). […] Chloroquine-induced endothelial cell cytotoxicity and stress is attenuated by agalsidase-β treatment. […] This suggests that endothelial cell injury may contribute to the failure of chloroquine as therapy for COVID-19 and may be at least in part related to causing dysfunction of the lysosomal enzyme α-galactosidase A.
33487787 It is suggested that the hyperinflammatory response and endothelial injury, especially in patients with severe disease, lead to a hypercoagulable state.
33488398 Together with endothelial lesions and hypercoagulability status, venous stasis completes the Virchow triad and considerably increases the prevalence of DVT and PE in critically ill COVID-19 patients, therefore raising questions regarding the optimal doses for thromboprophylaxis during ICU stay.
33489621 Interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are the key cytokines involved in mediating systemic inflammation and triggering endothelial dysfunction.
33492298 Acute tubular injury, cytokine storm induced systemic inflammatory response, endothelial injury and dysfunction are the main mechanisms of AKI.
33495740 PS may also promote thromboinflammation without circulating if expressed on the surface of endothelial cells, a condition that might only be documented if novel imaging techniques are developed.
33498225 Integrins on the surfaces of pneumocytes, endothelial cells and platelets may be vulnerable to CoV-2 virion binding. […] Binding of virions to integrins on endothelial cells could activate angiogenic cell signaling pathways; dysregulate integrin-mediated signaling pathways controlling developmental processes; and precipitate endothelial activation to initiate blood clotting.
33499234 An increasing amount of evidence suggests that lung endothelial cells play a critical role in the pathogenesis of both viruses. […] In this review, we discuss how infection with influenza or SARS-CoV-2 may induce endothelial dysfunction. […] Understanding the differences between the effects of these two viruses on lung endothelial cells will provide important insight to guide the development of therapeutics.
33502471 SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas.
33504351 The coronavirus infection 2019 (COVID-19) is associated with microvascular endothelial injury. […] Here, we report that syndecan-1, a component of endothelial glycocalyx, may reflect the disease state of COVID-19 related to endothelial injury. ratio gradually increased from 158 on hospitalization to 300 on Day 11, on which day the ventilator was withdrawn.
33504824 HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis).
33511992 ACE2 is important in the vascular system where it is found in arterial and venous endothelial cells and arterial smooth muscle cells in many vascular beds. […] In endothelial cells activation of the ACE2/Ang-(1-7)/Mas1 axis increases production of the vasodilator’s nitric oxide and prostacyclin’s and in vascular smooth muscle cells it inhibits pro-contractile and pro-inflammatory signaling. […] Endothelial ACE2 is cleaved by proteases, shed into the circulation and measured as soluble ACE2.
33512126 Autopsy material and medical history were studied and analyzed in a 20-year-old male patient who had died from COVID-19 infection with the development of acute SARS-CoV-2-associated hemorrhagic necrotizing encephalopathy in adults with obvious endothelial dysfunction confirmed by virological examination of the autopsy material. […] In this case, the brain structures displayed the main found histopathologic signs: widespread vasculitis (endotheliitis) with varying degrees of segmental and total endothelial destruction; thrombosis mainly of the vessels of the microcirculatory bed; parenchymal hemorrhagic necrosis and inflammation (encephalitis); severe necrobiotic damage to neurons.
33514354 The global spread of CoV2-SARS infection with a respiratory tropism, endothelial damages and procoagulant status endangers the SCD population.
33518461 During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. […] The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication.
33519510 Endothelial cells have emerged as key players in SARS-CoV-2 infection and COVID-19 inflammatory pathologies. […] Dysfunctional endothelial cells can promote chronic inflammation and disease processes like thrombosis, atherosclerosis, and lung injury. […] In endothelial cells, mitochondria regulate these inflammatory pathways via redox signaling, which is primarily achieved through mitochondrial reactive oxygen species (mtROS). […] Excess mtROS causes oxidative stress that can initiate and exacerbate senescence, a state that promotes inflammation and chronic endothelial dysfunction. […] In this review, we provide an overview of phenotypes mediated by mtROS in endothelial cells - such as mitochondrial dysfunction, inflammation, and senescence - as well as how these chronic states may be initiated by SARS-CoV-2 infection of endothelial cells. […] We also propose that SARS-CoV-2 activates mtROS-mediated feedback loops that cause long-term changes in host redox status and endothelial function, promoting cardiovascular disease and lung injury after recovery from COVID-19.
33521655 Proposed underlying mechanisms for these severe manifestations have encompassed immune dysregulation, including an anti-phospholipid syndrome-like state, complement activation, viral dissemination with direct systemic endothelial infection, viral RNAaemia with immunothrombosis, clotting pathway activation mediated by hypoxaemia, and immobility.
33523252 Systemic vascular involvement in COVID-19 has been identified in several patients: not only endothelial derangement and increased permeability are reported to be early hallmarks of organ damage in patients with COVID-19 but are also the most important cause of worsening of clinical conditions in severe cases of SARS-CoV-2 infection.
33523532 Here I discuss endothelial-epithelial co-operative in vivo responses producing first-line, humoral innate defence opportunities in human airways. […] By active venular endothelial gap formation, followed by transient yielding of epithelial junctions, non-sieved plasma macromolecules move from the microcirculation to the mucosal surface. […] Importantly, the endothelial responsiveness of the airway microcirculation differs distinctly from the relatively non-responsive, low-pressure pulmonary microcirculation that non-specifically, almost irreversibly, leaks plasma in life-threatening COVID-19.
33523608 SARS CoV-2 affects the microcirculation, causing endothelial cell swelling and damage (endotheliitis), microscopic blood clots (microthrombosis), capillary congestion, and damage to pericytes that are integral to capillary integrity and barrier function, tissue repair (angiogenesis), and scar formation.
33524803 Thrombotic microangiopathies are a group of disorders that are mainly related to endothelial dysfunction. […] This category of endothelial dysfunction results of several imbalances between platelets, endothelium and immune system, also cytokine production. […] To report cases with thrombotic thrombocytopenic purpura (TTP) and COVID-19 and review COVID-19 endothelial dysfunction literature.
33524866 Endothelial dysfunction has been highlighted as pivotal, irrespective of the mechanism involved in CAC.
33525228 Multiple mechanisms for developing pulmonary hypertension that have been postulated are i) concomitant worsening myocardial injury, ii) cytokine storm, endothelial injury, hypercoagulability attributing to development of venous thromboembolism, iii) and the presence of thrombotic microangiopathy.
33528647 This article addresses how guidance for ophthalmologists on managing patients with retinal disease receiving intravitreal injections of anti-vascular endothelial growth factor (VEGF) during the pandemic should be adapted to the local epidemic pressure, with more or less stringent measures implemented according to the ebb and flow of the pandemic.
33530272 The hypothesis of exacerbated damage caused by inflammatory and immunological endothelial systemic damage should further be explored to be able to delineate new possibilities in managing these conditions.
33534131 In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected.
33537347 The disease is characterized by endothelial dysfunction, platelet activation, thrombosis, coagulopathy, and multiple organ failure.
33539188 Here, we show that secretion of VWF from human umbilical vein endothelial cells (HUVEC) is significantly enhanced by 100,000 ng/ml of recombinant ferritin heavy chain protein (FHC). […] These observations suggest that a state of marked hyperferritinemia could promote thrombosis and organ injury by inducing endothelial VWF secretion and reducing the ADAMTS-13 activity.
33540179 Because in FH patients the level of low density lipoprotein cholesterol (LDL-C) is elevated from birth and it correlates with the degree of systemic endothelial dysfunction, both heterozygous FH (HeFH) patients and, in particular, homozygous FH (HoFH) patients have a dysfunctional endothelium prone to further damage by the direct viral attack and the hyper-inflammatory reaction typical of severe COVID-19.
33540664 Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood-brain barrier model.
33542837 The aim of the article is to justify the application of low-level laser therapy (LLLT) to prevent the development of endothelial dysfunction in COVID-19 patients. […] A literature review is conducted on mechanisms of vascular homeostasis regulation, biomodulating effect of laser light, and LLLT methods for preventing endothelial dysfunction. […] It was shown that LLLT is effective in preventing the development of endothelial dysfunction.
33542975 Several suspected pathophysiological mechanisms could explain the association between cardiovascular events and COVID-19 (role of systemic inflammatory response syndrome, endothelial dysfunction, activation of coagulation cascade leading to a hypercoagulability state, virus-induced secondary antiphospholipid syndrome).
33547062 PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers.
33548931 Coronavirus disease-2019 may predispose patients to VTE due to excessive inflammation, platelet activation, endothelial dysfunction, and hemostasis.
33550816 Background COVID-19 is a respiratory disease associated to thrombotic outcomes with coagulation and endothelial disorders.
33550983 The present review suggests treatment approaches for COVID-19 based on strategies used against ovarian cancer, which shares similar immunopathology and associated coagulation disorders.The chronicization of the hyperinflammatory cytokine storm in patients with severe COVID-19 highlights a defective resistance phase that leads to aspecific chronic inflammation, associated with oxidative stress, which impairs specific T-cell response, induces tissue and endothelial damage, and thrombosis associated with systemic effects that lead to severe multi-organ failure and death.
33551489 Magnesium deficiency increases endothelial cell susceptibility to oxidative stress, promotes endothelial dysfunction, reduces fibrinolysis and increases coagulation.
33551947 According to cell-type distribution analysis, nuclear expression of ACE2 was found in many neurons (both excitatory and inhibitory neurons) and some non-neuron cells (mainly astrocytes, oligodendrocytes, and endothelial cells) in the human middle temporal gyrus and posterior cingulate cortex. […] Except for the additional high expression of Ace2 in the olfactory bulb areas for spatial distribution as well as in the pericytes and endothelial cells for cell-type distribution, the distribution of Ace2 in the mouse brain was similar to that in the human brain.
33552890 In addition, iloprost antithrombotic effect, endothelial damage repairing and neo-angiogenesis activity could play a relevant role.
33553219 GPR4 is a pro-inflammatory G protein-coupled receptor (GPCR) highly expressed in vascular endothelial cells and serves as a “gatekeeper” to regulate endothelium-blood cell interaction and leukocyte infiltration.
33553222 Mechanistically, serving as functional receptors for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) mediates SARS-CoV-2 infection of endothelial cells (ECs) directly, leading to endothelial dysfunction and dysregulation of the renin-angiotensin system (RAS). […] More importantly, SARS-CoV-2 attacks the immune system, which results in excessive inflammation and perpetuates a vicious cycle of deteriorated endothelial dysfunction that further promotes inflammation. […] A better understanding of the underlying mechanisms of SARS-CoV-2 infection and the long-term monitoring of inflammatory factors and endothelial function should be considered in the follow-up of patients who have recovered from COVID-19 for early detection and prevention of atherosclerosis.
33554516 Midregional pro-adrenomedullin (MR-proADM) is a vasoactive peptide with key roles in reducing vascular hyperpermeability and thereby improving endothelial stability during infection.
33557911 Besides, the formation of NETs was detected by immunofluorescent staining and the cytotoxicity to vascular endothelial HUVEC cells was evaluated by CCK-8 assay. […] The pathological effect of the anaphylatoxin-NET axis on the damage of vascular endothelial cells could be relieved by recombinant carboxypeptidase B (CPB), a stable homolog of enzyme CPB2 which can degrade anaphylatoxins to inactive products.
33560456 The lungs with COVID-19 pneumonia revealed perivascular inflammation, an endothelial injury, microangiopathy, and an aberrant blood vessel neoformation by intussusceptive angiogenesis.
33560947 Coronavirus disease 2019 (COVID-19) may predispose patients to increased risk of venous thromboembolism (VTE) due to various pathophysiological mechanisms, including but not limited to endothelial injury, inflammation, cytokine-mediated microvascular damage, and reactive thrombocytosis.
33562030 Dysfunctions of endothelial cells and platelets are tightly linked in contributing to the systemic inflammatory response that appears to be both a cause and a consequence of COVID-19-associated coagulation disorders and thrombotic events.
33568895 In this cross-sectional, retrospective analysis of a single-provider outpatient clinic across multiple satellites, consecutive patients returning for intravitreal injections (IVIs) of anti-vascular endothelial growth factor or corticosteroids were identified as “delayed” or “undelayed” during a six-week study interval during the COVID-19 pandemic that closely following a mandated period of prohibited elective encounters.
33569392 Meanwhile, interactions of selectins and cytokines (e.g., IL-6 and TNF-α) with HS expressed on endothelial cells are crucial in controlling the recruitment of immune cells during inflammation.
33569525 The endothelial expression of angiotensin-converting enzyme-2 receptors makes it feasible that in patients with viraemia direct viral-toxicity to the endothelium of also the large arteries results in local thrombus formation.
33569769 Although growing evidence demonstrates a direct association between endotheliitis and severe COVID-19, the role of endothelial damage biomarkers has been scarcely studied. […] We investigated the relationship between circulating mid-regional proadrenomedullin (MR-proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS-CoV-2 infected patients.
33572570 Bilateral pneumonia, acute respiratory failure, systemic inflammation, endothelial dysfunction and coagulation activation are key features of severe COVID-19.
33574991 CAC is postulated to be one of the significant causes for sudden deaths in this pandemic, with infection of endothelial cells and subsequent endotheliitis through angiotensin-converting enzyme-2 receptors playing a key role in the pathogenesis.
33591004 We hypothesized that endothelial damage may lead to substantially increased concentrations of von Willebrand factor with subsequent relative deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13).