{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:17:50Z","timestamp":1791940670761,"version":"4.3.4"},"reference-count":155,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u20139 and Ang 1\u20137), 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.<\/jats:p>","DOI":"10.3390\/cells9071652","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T09:45:31Z","timestamp":1594374331000},"page":"1652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":235,"title":["COVID-19, Renin-Angiotensin System and Endothelial Dysfunction"],"prefix":"10.3390","volume":"9","author":[{"given":"Razie","family":"Amraei","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, Boston University Medical Campus, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Boston University Medical Campus, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1056\/NEJMoa030685","article-title":"A major outbreak of severe acute respiratory syndrome in Hong Kong","volume":"348","author":"Lee","year":"2003","journal-title":"N. 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