{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:43:23Z","timestamp":1790462603769,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FORICA (The Foundation for advanced Research In Hypertension and Cardiovascular diseases, foricaonlus.com)","award":["B\/2020\/0138"],"award-info":[{"award-number":["B\/2020\/0138"]}]},{"name":"FORICA (The Foundation for advanced Research In Hypertension and Cardiovascular diseases, foricaonlus.com)","award":["55813"],"award-info":[{"award-number":["55813"]}]},{"name":"Intesa San Paolo","award":["B\/2020\/0138"],"award-info":[{"award-number":["B\/2020\/0138"]}]},{"name":"Intesa San Paolo","award":["55813"],"award-info":[{"award-number":["55813"]}]},{"name":"CARIPARO to Department of Medicine-University of Padua","award":["B\/2020\/0138"],"award-info":[{"award-number":["B\/2020\/0138"]}]},{"name":"CARIPARO to Department of Medicine-University of Padua","award":["55813"],"award-info":[{"award-number":["55813"]}]},{"name":"SEED 2020 (Dept. of Biology)","award":["B\/2020\/0138"],"award-info":[{"award-number":["B\/2020\/0138"]}]},{"name":"SEED 2020 (Dept. of Biology)","award":["55813"],"award-info":[{"award-number":["55813"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Blockers of the renin-angiotensin system (RAS) have been reported to increase the angiotensin converting enzyme (ACE)2, the cellular receptor of SARS-CoV-2, and thus the risk and course of COVID-19. Therefore, we investigated if angiotensin (Ang) II and RAS blockers affected ACE2 expression and SARS-CoV-2 infectivity in human epithelial bronchial Calu-3 cells. By infectivity and spike-mediated cell\u2013cell fusion assays, we showed that Ang II acting on the angiotensin type 1 receptor markedly increased ACE2 at mRNA and protein levels, resulting in enhanced SARS-CoV-2 cell entry. These effects were abolished by irbesartan and not affected by the blockade of ACE-1-mediated Ang II formation with ramipril, and of ACE2- mediated Ang II conversion into Ang 1-7 with MLN-4760. Thus, enhanced Ang II production in patients with an activated RAS might expose to a greater spread of COVID-19 infection in lung cells. The protective action of Angiotensin type 1 receptor antagonists (ARBs) documented in these studies provides a mechanistic explanation for the lack of worse outcomes in high-risk COVID-19 patients on RAS blockers.<\/jats:p>","DOI":"10.3390\/ijms23095125","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T10:49:30Z","timestamp":1651661370000},"page":"5125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Angiotensin II Promotes SARS-CoV-2 Infection via Upregulation of ACE2 in Human Bronchial Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3885-7256","authenticated-orcid":false,"given":"Ilaria","family":"Caputo","sequence":"first","affiliation":[{"name":"Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3775-0011","authenticated-orcid":false,"given":"Brasilina","family":"Caroccia","sequence":"additional","affiliation":[{"name":"Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-5707","authenticated-orcid":false,"given":"Ilaria","family":"Frasson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine-DMM, University of Padua, 35121 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1680-9002","authenticated-orcid":false,"given":"Elena","family":"Poggio","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4362-4342","authenticated-orcid":false,"given":"Stefania","family":"Zamberlan","sequence":"additional","affiliation":[{"name":"Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-1995","authenticated-orcid":false,"given":"Margherita","family":"Morpurgo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-4086","authenticated-orcid":false,"given":"Teresa M.","family":"Seccia","sequence":"additional","affiliation":[{"name":"Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-1659","authenticated-orcid":false,"given":"Tito","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-0243","authenticated-orcid":false,"given":"Marisa","family":"Brini","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-9029","authenticated-orcid":false,"given":"Sara N.","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine-DMM, University of Padua, 35121 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-0931","authenticated-orcid":false,"given":"Gian Paolo","family":"Rossi","sequence":"additional","affiliation":[{"name":"Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1093\/eurheartj\/ehi114","article-title":"Myocardial Infarction Increases ACE2 Expression in Rat and 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