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Review
. 2022 Nov;26(5):351.
doi: 10.3892/mmr.2022.12867. Epub 2022 Oct 5.

Role of endothelial dysfunction in the severity of COVID‑19 infection (Review)

Tanya Kadiyska  1 , Ivan Tourtourikov  2 , Kristiyan Dabchev  2 , Radostina Cherneva  3 , Nikolay Stoynev  1 , Radka Hadjiolova  1 , Vanyo Mitev  2 , Demetrios A Spandidos  4 , Maria Adamaki  5 , Vassilis Zoumpourlis  5
Affiliations
Review

Role of endothelial dysfunction in the severity of COVID‑19 infection (Review)

Tanya Kadiyska et al. Mol Med Rep. 2022 Nov.

Abstract

COVID‑19 patients with severe infection have been observed to have elevated auto‑antibodies (AAs) against angiotensin II receptor type 1 (AT1R) and endothelin (ET) 1 receptor type A (ETAR), compared with healthy controls and patients with favorable (mild) infection. AT1R and ETAR are G protein‑coupled receptors, located on vascular smooth muscle cells, fibroblasts, immune and endothelial cells, and are activated by angiotensin II (Ang II) and ET1 respectively. AAs that are specific for these receptors have a functional role similar to the natural ligands, but with a more prolonged vasoconstrictive effect. They also induce the production of fibroblast collagen, the release of reactive oxygen species and the secretion of proinflammatory cytokines (including IL‑6, IL‑8 and TNF‑α) by immune cells. Despite the presence of AAs in severe COVID‑19 infected patients, their contribution and implication in the severity of the disease is still not well understood and further studies are warranted. The present review described the major vascular homeostasis systems [ET and renin‑angiotensin‑aldosterone system (RAAS)], the vital regulative role of nitric oxide, the AAs, and finally the administration of angiotensin II receptor blockers (ARBs), so as to provide more insight into the interplay that exists among these components and their contribution to the severity, prognosis and possible treatment of COVID‑19.

Keywords: COVID‑19; angiotensin; angiotensin‑converting enzyme; endothelin; renin; renin‑angiotensin‑aldosterone system.

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Conflict of interest statement

DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
The renin-angiotensin system, endothelins and COVID-19. Red arrows outline known pathological mechanisms. Red dashed arrows outline hypothetical pathological mechanisms. PPET, preproendothelin; ET, endothelin; BigET, big endothelin; ACE, angiotensin converting enzyme; MAS1, mitochondrial assembly protein 1; AT1R, angiotensin II receptor type 1; AT2R, angiotensin II receptor type 2; ETAR, endothelin-1 receptor type A.
See this image and copyright information in PMC

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