Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System
Identifieur interne : 000762 ( Main/Curation ); précédent : 000761; suivant : 000763Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System
Auteurs : Mahmoud Gheblawi ; Kaiming Wang ; Anissa Viveiros ; Quynh Nguyen ; Jiu-Chang Zhong ; Anthony J. Turner [Royaume-Uni] ; Mohan K. Raizada ; Maria B. Grant ; Gavin Y. OuditSource :
- Circulation Research [ 0009-7330 ] ; 2020.
Abstract
ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor.
Url:
DOI: 10.1161/CIRCRESAHA.120.317015
PubMed: 32264791
PubMed Central: 7188049
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Mahmoud Gheblawi<affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff4">Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, China (J.-C.Z.)</nlm:aff><wicri:noCountry code="subfield">China (J.-C.Z.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff6">Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville (M.K.R.)</nlm:aff><wicri:noCountry code="subfield">Gainesville (M.K.R.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff7">Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham (M.B.G.).</nlm:aff><wicri:noCountry code="subfield">University of Alabama at Birmingham (M.B.G.).</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System</title><author><name sortKey="Gheblawi, Mahmoud" sort="Gheblawi, Mahmoud" uniqKey="Gheblawi M" first="Mahmoud" last="Gheblawi">Mahmoud Gheblawi</name><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Wang, Kaiming" sort="Wang, Kaiming" uniqKey="Wang K" first="Kaiming" last="Wang">Kaiming Wang</name><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Viveiros, Anissa" sort="Viveiros, Anissa" uniqKey="Viveiros A" first="Anissa" last="Viveiros">Anissa Viveiros</name><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Nguyen, Quynh" sort="Nguyen, Quynh" uniqKey="Nguyen Q" first="Quynh" last="Nguyen">Quynh Nguyen</name><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Zhong, Jiu Chang" sort="Zhong, Jiu Chang" uniqKey="Zhong J" first="Jiu-Chang" last="Zhong">Jiu-Chang Zhong</name><affiliation><nlm:aff id="aff4">Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, China (J.-C.Z.)</nlm:aff><wicri:noCountry code="subfield">China (J.-C.Z.)</wicri:noCountry></affiliation></author><author><name sortKey="Turner, Anthony J" sort="Turner, Anthony J" uniqKey="Turner A" first="Anthony J." last="Turner">Anthony J. 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Grant</name><affiliation><nlm:aff id="aff7">Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham (M.B.G.).</nlm:aff><wicri:noCountry code="subfield">University of Alabama at Birmingham (M.B.G.).</wicri:noCountry></affiliation></author><author><name sortKey="Oudit, Gavin Y" sort="Oudit, Gavin Y" uniqKey="Oudit G" first="Gavin Y." last="Oudit">Gavin Y. Oudit</name><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32264791</idno><idno type="pmc">7188049</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188049</idno><idno type="RBID">PMC:7188049</idno><idno type="doi">10.1161/CIRCRESAHA.120.317015</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000887</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000887</idno><idno type="wicri:Area/Pmc/Curation">000887</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000887</idno><idno type="wicri:Area/Pmc/Checkpoint">000652</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000652</idno><idno type="wicri:Area/Ncbi/Merge">000D05</idno><idno type="wicri:Area/Ncbi/Curation">000D05</idno><idno type="wicri:Area/Ncbi/Checkpoint">000D05</idno><idno type="wicri:doubleKey">0009-7330:2020:Gheblawi M:angiotensin:converting:enzyme</idno><idno type="wicri:Area/Main/Merge">000763</idno><idno type="wicri:Area/Main/Curation">000762</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System</title><author><name sortKey="Gheblawi, Mahmoud" sort="Gheblawi, Mahmoud" uniqKey="Gheblawi M" first="Mahmoud" last="Gheblawi">Mahmoud Gheblawi</name><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Wang, Kaiming" sort="Wang, Kaiming" uniqKey="Wang K" first="Kaiming" last="Wang">Kaiming Wang</name><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Viveiros, Anissa" sort="Viveiros, Anissa" uniqKey="Viveiros A" first="Anissa" last="Viveiros">Anissa Viveiros</name><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Nguyen, Quynh" sort="Nguyen, Quynh" uniqKey="Nguyen Q" first="Quynh" last="Nguyen">Quynh Nguyen</name><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author><author><name sortKey="Zhong, Jiu Chang" sort="Zhong, Jiu Chang" uniqKey="Zhong J" first="Jiu-Chang" last="Zhong">Jiu-Chang Zhong</name><affiliation><nlm:aff id="aff4">Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, China (J.-C.Z.)</nlm:aff><wicri:noCountry code="subfield">China (J.-C.Z.)</wicri:noCountry></affiliation></author><author><name sortKey="Turner, Anthony J" sort="Turner, Anthony J" uniqKey="Turner A" first="Anthony J." last="Turner">Anthony J. Turner</name><affiliation wicri:level="4"><nlm:aff id="aff5">School of Biomedical Sciences, University of Leeds, United Kingdom (A.J.T.)</nlm:aff><orgName type="university">Université de Leeds</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation></author><author><name sortKey="Raizada, Mohan K" sort="Raizada, Mohan K" uniqKey="Raizada M" first="Mohan K." last="Raizada">Mohan K. Raizada</name><affiliation><nlm:aff id="aff6">Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville (M.K.R.)</nlm:aff><wicri:noCountry code="subfield">Gainesville (M.K.R.)</wicri:noCountry></affiliation></author><author><name sortKey="Grant, Maria B" sort="Grant, Maria B" uniqKey="Grant M" first="Maria B." last="Grant">Maria B. Grant</name><affiliation><nlm:aff id="aff7">Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham (M.B.G.).</nlm:aff><wicri:noCountry code="subfield">University of Alabama at Birmingham (M.B.G.).</wicri:noCountry></affiliation></author><author><name sortKey="Oudit, Gavin Y" sort="Oudit, Gavin Y" uniqKey="Oudit G" first="Gavin Y." last="Oudit">Gavin Y. Oudit</name><affiliation><nlm:aff id="aff1">From the Department of Physiology (M.G., A.V., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff2">Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (K.W., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (M.G., K.W., A.V., Q.N., G.Y.O.)</nlm:aff><wicri:noCountry code="subfield">G.Y.O.)</wicri:noCountry></affiliation></author></analytic><series><title level="j">Circulation Research</title><idno type="ISSN">0009-7330</idno><idno type="eISSN">1524-4571</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. <italic>ACE2</italic> is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of <italic>Ace2</italic>, Ang 1–7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Patel, Vb" uniqKey="Patel V">VB Patel</name></author><author><name sortKey="Zhong, Jc" uniqKey="Zhong J">JC Zhong</name></author><author><name sortKey="Grant, Mb" uniqKey="Grant M">MB Grant</name></author><author><name sortKey="Oudit, Gy" uniqKey="Oudit G">GY Oudit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tipnis, Sr" uniqKey="Tipnis S">SR Tipnis</name></author><author><name sortKey="Hooper, Nm" uniqKey="Hooper N">NM Hooper</name></author><author><name sortKey="Hyde, R" uniqKey="Hyde R">R Hyde</name></author><author><name sortKey="Karran, E" 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