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Reviews in Cardiovascular Medicine  2020, Vol. 21 Issue (3): 315-319     DOI: 10.31083/j.rcm.2020.03.126
Special Issue: Utilizing Technology in the COVID 19 era
Review | Next articles
Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy
Jun Zhang1, *(), Kristen M. Tecson1, Peter A. McCullough1, 2, 3
1Baylor Heart and Vascular Institute, Dallas, TX 75226, USA
2Baylor University Medical Center, Dallas, TX 75226, USA
3Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX 75226, USA
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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). Upon viral infection of ECs by severe acute respiratory syndrome coronarvirus 2 (SARS-CoV-2), ECs become activated and dysfunctional. 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. Higher levels of acute phase reactants (IL-6, C-reactive protein, and D-dimer) are also associated with SARS-CoV-2 infection. 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. Here we present an update on ED-relevant vasculopathy in COVID-19. Further research for ED in COVID-19 patients is warranted to understand therapeutic opportunities.

Key words:  COVID-19      coagulation      cytokines      endothelial dysfunction      SARS-CoV-2      von Willebrand factor      thrombosis     
Submitted:  02 July 2020      Revised:  10 August 2020      Accepted:  12 August 2020      Published:  30 September 2020     
Fund: Baylor Health Care System Foundation
*Corresponding Author(s):  Jun Zhang     E-mail:

Cite this article: 

Jun Zhang, Kristen M. Tecson, Peter A. McCullough. Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy. Reviews in Cardiovascular Medicine, 2020, 21(3): 315-319.

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Fig. 1.  Schematic diagram depicting endothelial dysfunction (ED) contributing to COVID-19-associated vascular inflammation and coagulopathy. The angiotensin converting enzyme 2 (ACE2) receptor is widely expressed on endothelial cells in the lung, heart, kidney, and intestine, allowing endothelial cells (EC) to be infected by severe acute respiratory syndrome coronarvirus 2 (SARS-CoV-2). The sequence of cellular events leading to ED begins (as early as) immediately for type I EC activation, followed by type II EC activation, EC apoptosis, and EC necrosis. Type I EC activation does not require de novo protein synthesis by means of immediately releasing pro-stored proteins such as von Willebrand factor (vWF), P-selectin, thrombin, and histamine. Conversely, type II EC activation requires de novo protein synthesis by means of releasing new proteins such as vWF, Tissue factor, fibrinogen, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 (IL-1), monocyte chemoattractant protein-1, (MCP-1), and C-reactive protein. Endothelial apoptosis results in endothelial detachment by anoikis & denudation of basement membrane, whereas endothelial necrosis results in further release of thrombomudulin and vWF. Finally, leukocyte adhesion molecules, pro-inflammatory cytokines (IL-1, IL-6, and TNF), chemokines (MCP-1), together with pro-coagulant molecules contribute to COVID-19 –associated inflammation and coagulopathy.

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