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.