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ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein\u2013coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2\/Ang-(1-7)\/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.<\/jats:p>","DOI":"10.1042\/cs20200570","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T09:47:22Z","timestamp":1602668842000},"page":"2581-2595","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["ACE2 as therapeutic agent"],"prefix":"10.1042","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4211-6514","authenticated-orcid":false,"given":"Qiuhong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria\u00a0B.","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama College of Medicine, Birmingham, AL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine\u00a0M.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan\u00a0K.","family":"Raizada","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"2021113011162804300_B1","doi-asserted-by":"publisher","first-page":"C82","DOI":"10.1152\/ajpcell.00287.2006","article-title":"Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system","volume":"292","author":"Mehta","year":"2007","journal-title":"Am. 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