, Navarro S SUMMARY: Coronavirus disease 19 (COVID-19) is a pandemic originating in Wuhan, China, in December 2019. These various disturbances in endothelial function, depicted in the middle part of the diagram, lead to end organ damage including adult respiratory distress syndrome and thrombosis in the lungs, predispose to plaque rupture and thrombosis in coronary arteries, and affect the microvasculature leading to myocardial ischaemia and damage. Endothelium. , Warner SJC , Madison JA d’Alessandro E The dynamic nature of vascular endothelial functions. , Pyrgakis VN Under physiological circumstances, the endothelial gateway selectively regulates endothelial permeability and fosters vascular integrity. For permissions, please email: journals.permissions@oup.com. , Loomba R , d Birinyi LK. The endothelial monolayer that lines the intima of arteries, veins, and microvessels measures up to 7000 m 2 in surface area. , Green C The endothelial surface bears thrombomodulin, which binds thrombin and stimulates the protein C–protein S anticoagulant axis.1,3 The endothelial cell can also express a tissue factor pathway inhibitor that can antagonize triggering of thrombosis by the potent procoagulant protein tissue factor.7. 1 The endothelium possesses a series of remarkable properties that contribute capitally to homeostasis (Figure 1, left). , Cleuren A , Lu H , Nagel J , Rayes R , Klein CE , Vavouranakis E , Pfefferle S "When the virus damages the inside of the blood vessel and shreds the lining, that's like the ice after a hockey game," noted Dr. Li, a researcher and founder of the Angiogenesis Foundation. , Wu W Downstream of IL-1, antibodies that interfere with IL-6 signalling have also shown signs of benefit in some but not all preliminary studies, although this as well as other anticytokine therapies may entail an increased risk of superinfection.59,60 Other anti-IL-6 strategies also warrant consideration.61 Upon inflammatory stimulation, vascular endothelial and smooth muscle cells produce large amounts of IL-6; thus, blocking signalling of this distal mediator can limit local vascular amplification of inflammatory responses, including in the lung. , Loscalzo J , Dupont S , Schwartz SM Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. , Dolianitis K Ackermann M , Henke P The research suggests the potential to therapeutically target activation, rather than infection of the endothelium, as a strategy for resolving coagulation and inflammatory COVID … , Gerakari S , Ji Y-X , Kanonidis I IL-6 also triggers the acute phase response, boosting fibrinogen and PAI-1 production, and thus favours clot formation and persistence (Figure 2). COVID-19 can cause symptoms that go well beyond the lungs, from strokes to organ failure. While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host. , Spicer JD , Ullrich V , Eaton JW NIH , Weitz J , Stark H , Sipsas N, , Moore HB , Scavone G , Narazaki M Thus, disordered endothelial homeostasis provoked by cytokines provides a common thread in numerous complications of COVID-19.13,50–52. Impaired endothelial viability can promote sloughing of endothelial cells and their death by various mechanisms including pyroptosis and apoptosis.34,35 Among the stimuli for these pathways of programmed cell death are proinflammatory cytokines and reactive oxygen species. , Schröder AS , Wang Y , Bézie Y , Ruggeri A , De Luca G , Triposkiadis F , Mourad J-J COVID-19 is, in the end, an endothelial disease The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis. , Palacios-Callender M , Hajjar K , Michalis L , Lüscher TF. , Capretti G This unifying hypothesis can help to understand the complex pathophysiology of this current plague and may also help to inform our therapeutic approaches to combatting the consequences of SARS-CoV-2 infection. , Massberg S , Ye P , Malinski T Horby P , Bode C , Liao X , Haynes R Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries. , Rege K , Kremers B , Crawford JM , Araujo HA USA.gov. Franck G In small vessels, such as those that embrace alveoli in the lung, this impaired barrier function can lead to capillary leak. The endothelial cell usually possesses little procoagulant potential. , Brovkovich V Clipboard, Search History, and several other advanced features are temporarily unavailable. , Shvartz E , Mannucci PM , Yuan Y , Gautier A COVID-19; SARS-CoV-2; coagulation; cytokines; endothelial dysfunction; thrombosis; von Willebrand factor. , Sun W Under normal conditions, the endothelial cells promote tonic vasodilatation through the well-known mechanism of production of the vasodilatory gas nitric oxide from l-arginine via the activity of endothelial nitric oxide synthase.17 The endothelial cell can also elaborate diverse hyperpolarizing factors that promote relaxation of smooth muscle and hence dilatation of muscular arteries. , Ye Z , Costantino S , Zeerleder SS 1.4.2. , Angelidis C Libby P. SARS-CoV-2 infection and vascular dysfunction In health, the vascular endothelium maintains homeostasis through regulation of immune competence, inflammatory equilibrium, tight junctional barriers, hemodynamic stability as well as optimally … , Libby P. Wang J The pivotal roles of these proinflammatory mediators in host defences render these initial results plausible and promising.  |  , Lazareth I , Ma X , Walter S , Alyonycheva T , Islam N , Zhou Y , Ceska M , Borczuk A , van den Kerkhof D , Chen G IL-1 not only induces leucocyte adhesion molecules but, by reducing VE-cadherin production, can contribute to impaired endothelial barrier function and thus capillary leak, a major issue that complicates COVID-19 pneumonitis.47 Agents that inhibit the inflammasome–IL-1β–IL-6 pathway may thus comprise a more endothelial-directed approach to treatment of COVID-19. , Paschen H-R , Xiao B Quillard T , Lüscher TF , Della-Torre E , Syrigos K, , Gayle R , Zhu L All rights reserved. , Maliszewski C. Yang ZH , Béa ML , Stulz P Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. Colchicine may act in part as an inhibitor of the assembly of the inflammasome. , Heinrich F , Laschet J COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19. When the endothelial cells undergo the cytopathic effect of a viral infection such as SARS-CoV-2, or encounter pathogen-associated molecular patterns (PAMPs) derived from viruses or bacteria such as lipopolysaccharide, proinflammatory cytokines such as IL-1 or TNF, or damage-associated molecular patterns (DAMPs) derived from dead or dying cells, the endothelial cells become activated. , Vogler TO , Felton T These molecules include intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-1, CD106). , Goudevenos J Yet Covid-19 can affect … , Hoylaerts M Canakinumab, a selective IL-1β antibody, has a much longer biological half-life than anakinra, rendering it less readily reversible. , Volpe M Conflict of interest: P.L. It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems, in particular the lungs, heart, brain, kidney, and vasculature. , Mantovani A. Kang S , Labugger R In another New England Journal of …  |  , Han M As noted above, the normal endothelial cells also secrete PGI2 that, in addition to its antiaggregatory effects on platelets, potently vasodilates.18 This array of vasodilatory actions can also modulate moment-to-moment local blood flow in a paracrine fashion. Integrins associated with the endothelial surface also participate in these adhesive interactions and furnish cognate ligands for the adhesion molecules.25 Once tightly bound to the endothelial surface, chemoattractant cytokines of various classes can beckon the bound cells to traverse the endothelial monolayer and enter tissues where they can combat invaders or contribute to tissue repair.26. , Bell J , Dolleman SC The endothelium serves as one of the main targets of the SARS-CoV-2 virus, and endothelial dysfunction largely determines the pathogenesis and clinical outcome in COVID-19 (Teuwen et al., 2020). Epub 2020 Sep 12. Deftereos SG 2020 Dec 6;21(23):9309. doi: 10.3390/ijms21239309. COVID-19 can cause symptoms that go well beyond the lungs, from strokes to organ failure. , Blair CN Vascular endothelial cell pathology in COVID-19 The vascular pathology of COVID-19 is a topic of great interest [ 37 ]. , Dauriat G 4,5. 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This site needs JavaScript to work properly. , Li H. Cavalli G 20 Of particular note, there is also evidence of SARS-CoV-2 infection of vascular endothelial cells (ECs). , eds. Endothelium-directed therapies in COVID-19. , van Paridon P , Battista R , Lütgehetmann M , Kilo J , Migdalis I , Henskens YMC , Stang A, Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) has affected millions of people globally. , Soriano EM , Looney MR Sloughing of endothelial cells uncovers the thrombogenic basement membrane. , Nydam TL , Toutouzas KP , Colotta F , Lin L We report a case of COVID-19 with acute ischemic stroke. Xiong S The vascular endothelium provides the crucial interface between the blood compartment and tissues. , Tassan Din C In this study, we sought to investigate the status of vascular endothelial function in COVID-19 patients from a non-invasive approach. , Persson O , Knight JS The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection. , Becker H Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19. , Fu B , ten Cate H , Wang X , Shi H , Zhao Y-C , Ciceri F , Crijns HJGM , Yang Y The endothelial monolayer that lines the intima of arteries, veins, and microvessels measures up to 7000 m2 in surface area.1 The endothelium possesses a series of remarkable properties that contribute capitally to homeostasis (Figure 1, left). Angiotensin II is one of the strongest stimulants of Na + /H + exchanger (NHE). Corresponding author. © The Author(s) 2020. , Soares MP , Posnett D This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (, EMPEROR-REDUCED reigns while EMPERIAL whimpers, Management of refractory angina: an update, Noise and cardiovascular risk: nighttime aircraft noise acutely triggers cardiovascular death, Time to revisit implantable cardioverter-defibrillator implantation criteria in women, Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome, The endothelium participates pivotally in thrombosis and fibrinolysis, The endothelial vasodilator/vasoconstrictor balance, Antioxidant/pro-oxidant balance in the endothelium, Cytokine storm: a perfect storm in COVID-19, Endothelial functions as a therapeutic target, https://doi.org/10.1093/eurheartj/ehaa623, https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model, Receive exclusive offers and updates from Oxford Academic, [Study of the functional state of the periodontium in older persons and its correction by means of oral hygiene. , Linsell L , Soehnlein O Peter Libby, Thomas Lüscher, COVID-19 is, in the end, an endothelial disease, European Heart Journal, Volume 41, Issue 32, 21 August 2020, Pages 3038–3044, https://doi.org/10.1093/eurheartj/ehaa623. 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