Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases.
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This review summarizes and discusses the structure and multiple functions of ACE2 and the relevance of this key enzyme in disease pathogenesis.Abstract:
Angiotensin-converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system, and functions as the key SARS coronavirus receptor and stabilizer of neutral amino acid transporters. ACE2 catalyzes the conversion of angiotensin II to angiotensin 1-7, thereby counterbalancing ACE activity. Accumulating evidence indicates that the enzymatic activity of ACE2 has a protective role in cardiovascular diseases. Loss of ACE2 can be detrimental, as it leads to functional deterioration of the heart and progression of cardiac, renal, and vascular pathologies. Recombinant soluble human ACE2 protein has been demonstrated to exhibit beneficial effects in various animal models, including cardiovascular diseases. ACE2 is a multifunctional enzyme and thus potentially acts on other vasoactive peptides, such as Apelin, a vital regulator of blood pressure and myocardium contractility. In addition, ACE2 is structurally a chimeric protein that has emerged from the duplication of 2 genes: homology with ACE at the carboxypeptidase domain and homology with Collectrin in the transmembrane C-terminal domain. ACE2 has been implicated in the pathology of Hartnup's disease, a disorder of amino acid homeostasis, and, via its function in amino acid transport, it has been recently revealed that ACE2 controls intestinal inflammation and diarrhea, thus regulating the gut microbiome. This review summarizes and discusses the structure and multiple functions of ACE2 and the relevance of this key enzyme in disease pathogenesis.read more
Citations
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The pivotal link between ACE2 deficiency and SARS-CoV-2 infection.
TL;DR: It is suggested that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions, and recombinant ACE2, angiotensin1-7 and angiotsin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.
Journal ArticleDOI
Angiotensin-converting enzyme 2 and angiotensin 1–7: novel therapeutic targets
Fan Jiang,Jianmin Yang,Yongtao Zhang,Mei Dong,Shuangxi Wang,Qunye Zhang,Fang Fang Liu,Kai Zhang,Cheng Zhang +8 more
TL;DR: The ACE2-mediated catabolism of angiotensin II is likely to have a major role in cardiovascular protection, whereas the relevant functions and signalling mechanisms of actions induced by ang Elliotensin 1–7 have not been conclusively determined.
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Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis.
TL;DR: SARS‐CoV‐2 coronavirus infection ranges from asymptomatic through to fatal COVID‐19 characterized by a ‘cytokine storm’ and lung failure and Vitamin D deficiency has been postulated as a determinant of severity.
Journal ArticleDOI
ACE2 - from the renin-angiotensin system to gut microbiota and malnutrition.
Thomas Perlot,Josef M. Penninger +1 more
TL;DR: ACE2 modulates innate immunity and influences the composition of the gut microbiota, which can explain diarrhea and intestinal inflammation observed in Hartnup disorder, Pellagra, or under conditions of severe malnutrition.
Journal ArticleDOI
Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress
TL;DR: Western blotting and qPCR show that ACE2 expression is increased under conditions of cell stress, including hypoxic conditions, IL (interleukin)-1β treatment and treatment with the AMP mimic AICAR.
References
More filters
Journal ArticleDOI
The Genome Sequence of the SARS-associated Coronavirus
Marco A. Marra,Steven J.M. Jones,Caroline R. Astell,Robert A. Holt,Angela Brooks-Wilson,Yaron S.N. Butterfield,Jaswinder Khattra,Jennifer Asano,Sarah Barber,Susanna Y. Chan,Alison Cloutier,Shaun M. Coughlin,Doug Freeman,Noreen Girn,Obi L. Griffith,Stephen Leach,Michael Mayo,Helen McDonald,Stephen B. Montgomery,Pawan Pandoh,Anca Petrescu,A. Gordon Robertson,Jacqueline E. Schein,Asim Siddiqui,Duane E. Smailus,Jeff M. Stott,George S. Yang,Francis A. Plummer,Anton Andonov,Harvey Artsob,Nathalie Bastien,Kathy Bernard,Timothy F. Booth,Donnie Bowness,Martin Czub,Michael Drebot,Lisa Fernando,Ramon Flick,Michael Garbutt,Michael Gray,Allen Grolla,Steven M. Jones,Heinz Feldmann,Adrienne Meyers,Amin Kabani,Yan Li,Susan Normand,Ute Ströher,Graham A. Tipples,Shaun Tyler,Robert Vogrig,Diane M. Ward,Brynn Watson,Robert C. Brunham,Mel Krajden,Martin Petric,Danuta M. Skowronski,Chris Upton,Rachel L. Roper +58 more
TL;DR: The genome sequence reveals that the severe acute respiratory syndrome–associated coronavirus known as the Tor2 isolate is only moderately related to other known coronaviruses, andylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronavirs.
Journal ArticleDOI
A Human Homolog of Angiotensin-converting Enzyme CLONING AND FUNCTIONAL EXPRESSION AS A CAPTOPRIL-INSENSITIVE CARBOXYPEPTIDASE
Sarah R. Tipnis,Nigel M. Hooper,Ralph J. Hyde,Eric H. Karran,Gary Christie,Anthony J. Turner +5 more
TL;DR: A novel human zinc metalloprotease that has considerable homology to human angiotensin-converting enzyme (ACE) (40% identity and 61% similarity) has been identified.
Journal ArticleDOI
Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor
Fang Li,Wenhui Li,Wenhui Li,Michael Farzan,Michael Farzan,Stephen C. Harrison,Stephen C. Harrison +6 more
TL;DR: The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.
Journal ArticleDOI
Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas.
Robson A.S. Santos,Ana Cristina Simões e Silva,Christine Maric,Denise M. R. Silva,Raquel Pillar Machado,Insa de Buhr,Silvia Heringer-Walther,Sérgio Veloso Brant Pinheiro,Myriam Teresa Lopes,Michael Bader,Elizabeth Pereira Mendes,Virgina Soares Lemos,Maria José Campagnole-Santos,Heinz-Peter Schultheiss,Robert C. Speth,Thomas Walther +15 more
TL;DR: Findings identify Mas as a functional receptor for Ang-(1–7) and provide a clear molecular basis for the physiological actions of this biologically active peptide.
Journal ArticleDOI
Angiotensin-converting enzyme 2 is an essential regulator of heart function
Michael A. Crackower,Renu Sarao,Renu Sarao,Gavin Y. Oudit,Gavin Y. Oudit,Chana Yagil,Ivona Kozieradzki,Ivona Kozieradzki,Sam E. Scanga,Antonio J. Oliveira-dos-Santos,Joan da Costa,Liyong Zhang,York Pei,James W. Scholey,Carlos M. Ferrario,Armen S. Manoukian,Mark C. Chappell,Peter H. Backx,Peter H. Backx,Yoram Yagil,Josef M. Penninger +20 more
TL;DR: These genetic data for ACE2 show that it is an essential regulator of heart function in vivo and targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart.
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