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COVID-19, Renin-Angiotensin System and Endothelial Dysfunction.
Cells. 2020 07 09; 9(7)C

Abstract

The newly emergent novel coronavirus disease 2019 (COVID-19) outbreak, which is caused by SARS-CoV-2 virus, has posed a serious threat to global public health and caused worldwide social and economic breakdown. Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1-9 and Ang 1-7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. Once inside the host cells, SARS-CoV-2 induces acute respiratory distress syndrome (ARDS), stimulates immune response (i.e., cytokine storm) and vascular damage. SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. We also surveyed the roles of cell adhesion molecules (CAMs), including CD209L/L-SIGN and CD209/DC-SIGN in SARS-CoV-2 infection and other related viruses. Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19.

Links

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Authors+Show Affiliations

Amraei R
Department of Pathology, School of Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Rahimi N
Department of Pathology, School of Medicine, Boston University Medical Campus, Boston, MA 02118, USA.

MeSH

Angiotensin IAngiotensin-Converting Enzyme 2BetacoronavirusCOVID-19Cell Adhesion MoleculesCoronavirus InfectionsEndothelium, VascularHost Microbial InteractionsHumansPandemicsPeptidyl-Dipeptidase APneumonia, ViralRenin-Angiotensin SystemSARS-CoV-2Signal Transduction

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

32660065

Clinical Trial Links

Assessment of the Efficacy of Calcium Dobesilate vs. Placebo on SARS-CoV-2 Viral Load Amongst Outpatients With COVID-19.

Citation

Amraei, Razie, and Nader Rahimi. "COVID-19, Renin-Angiotensin System and Endothelial Dysfunction." Cells, vol. 9, no. 7, 2020.
Amraei R, Rahimi N. COVID-19, Renin-Angiotensin System and Endothelial Dysfunction. Cells. 2020;9(7).
Amraei, R., & Rahimi, N. (2020). COVID-19, Renin-Angiotensin System and Endothelial Dysfunction. Cells, 9(7). https://doi.org/10.3390/cells9071652
Amraei R, Rahimi N. COVID-19, Renin-Angiotensin System and Endothelial Dysfunction. Cells. 2020 07 9;9(7) PubMed PMID: 32660065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - COVID-19, Renin-Angiotensin System and Endothelial Dysfunction. AU - Amraei,Razie, AU - Rahimi,Nader, Y1 - 2020/07/09/ PY - 2020/06/03/received PY - 2020/07/04/revised PY - 2020/07/07/accepted PY - 2020/7/15/entrez PY - 2020/7/15/pubmed PY - 2020/7/25/medline KW - ACE2 KW - CD209L KW - L-SIGN KW - SARS-CoV-2 KW - endothelial cell injury KW - endothelial dysfunction JF - Cells JO - Cells VL - 9 IS - 7 N2 - The newly emergent novel coronavirus disease 2019 (COVID-19) outbreak, which is caused by SARS-CoV-2 virus, has posed a serious threat to global public health and caused worldwide social and economic breakdown. Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1-9 and Ang 1-7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. Once inside the host cells, SARS-CoV-2 induces acute respiratory distress syndrome (ARDS), stimulates immune response (i.e., cytokine storm) and vascular damage. SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. We also surveyed the roles of cell adhesion molecules (CAMs), including CD209L/L-SIGN and CD209/DC-SIGN in SARS-CoV-2 infection and other related viruses. Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19. SN - 2073-4409 UR - https://www.unboundmedicine.com/medline/citation/32660065/COVID_19_Renin_Angiotensin_System_and_Endothelial_Dysfunction_ DB - PRIME DP - Unbound Medicine ER -