Abstract
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.
Highlights
Great attention has been paid to endothelial dysfunction (ED) in coronavirus disease 2019 (COVID-19)
The sequence of cellular events leading to ED may be described as (1) reversible type I endothelial activation, which represents an immediate event of ED that release prostored proteins von Willebrand factor (vWF), P-electin, thrombin, histamine, etc; (2) reversible type II endothelial activation, which synthesizes new proteins such as CRP, fibrinogen, vWF, tissue factor, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), IL-1, and MCP-1; (3) irreversible endothelial apoptosis, which leads to detachment of endothelial cells (ECs) by anoikis; and (4) irreversible endothelial necrosis
While anticoagulant and procoagulant activities are balanced in tissue factor, thromboxane A2 (TXA2), the imbalance associated with the loss of anticoagulant molecules and synthesis of procoagulant molecules favors thrombosis (Zhang et al, 2010)
Summary
Endothelial dysfunctioned (ED) involves functional phenotype modifications in order to regulate hemostasis and thrombosis and control inflammatory reactions within blood vessels (Gimbrone and García-Cardeña, 2016). In regard to an acute pro-inflammatory response, endothelial activation, in small vessels, is divided into two types: type I endothelial activation (stimulation) and type 2 endothelial activation, which involve effector proteins including class-II major histocompatibility antigens, E-selectin, vascular cell adhesion molecule-1 1), tissue factor, interleukin-8 (IL-8) and monocyte chemotractant protein-1 (MCP-1) (Gimbrone and García-Cardeña, 2016). These proteins are detectable in the microvasculature at sites of inflammation. ED consists of type 1 and type II endothelial activation, as well as endothelial cell injury (e.g., endothelial cell apoptosis and necrosis), as demonstrated by pathological findings in animal studies (Zhang et al, 2012). The following terms ''endothelial activation'', ''endothelial dysfunction'', ''endothelial damage'' and ''endothelial injury'' may be used interchangeably (Zhang et al, 2017)
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