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

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. Contents1. Introduction 2. How does vasoconstriction occur? 3. Endothelin and endothelin receptors 4. RAAS 5. NO 6. AT1R and ETAR auto-antibodies 7. Conclusions

A Novel Human Extravascular Monocyte Subset with Antiviral Functions Is Crucial for Resolving Lung Tissue Infection

“…Downregulation of several transcripts coding for activation markers (CD69), MHC genes (HLA-DPB1, HLA-C) and major proteins regulating cellular metabolism and transcription (HSP90AA1, RPL13A) was reflective of endothelial dysfunction and stress (Fig. 6 L); consistent with human patient reports and animal studies (Kadiyska et al, 2022;Otifi and Adiga, 2022;Qin et al, 2021;Xu et al, 2023). At 12 dpi, venous endothelial cells upregulated expression of mitochondrial genes, which was similar to the transcriptomic pattern of activated fibroblasts.…”

Recovery from antibody-mediated biliary ductopenia and multiorgan inflammation after COVID-19 vaccination

“…Ideally, the vaccine simulates an actual infection by mimicking the virus and the immune system reacts similarly to an actual infection. However, increased AT1R antibody levels have been observed in cases of multiorgan tissue damage and acute respiratory distress syndrome in COVID-19 patients 31 , 32 . We found that the AT1R antibody level in this patient was elevated (peak, 166.61 U/mL; positive, >17 U/mL) (Fig.…”

Antibodies against angiotensin II receptor type 1 and endothelin A receptor are increased in COVID-19 patients

“…The generation of autoantibodies targeting GPCRs, including AT1R and ETAR, has been demonstrated during COVID-19, but their contribution to disease pathogenesis is not well understood ( 5 ). Several studies found increased levels of AT1R and ETAR in severe COVID-19 disease course compared to mild disease or controls ( 1 – 3 ).…”

“…In COVID-19 patients, AT1R and ETAR titers did not correlate with baseline inflammatory markers or diffusion capacity, cognitive impairment, or fatigue measured at 3 months follow-up. The generation of autoantibodies targeting GPCRs, including AT1R and ETAR, has been demonstrated during COVID-19, but their contribution to disease pathogenesis is not well understood (5). Several studies found increased levels of AT1R and ETAR in severe COVID-19 disease course compared to mild disease or controls (1)(2)(3).…”