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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Journal ArticleDOI
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.
Journal ArticleDOI
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
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Journal ArticleDOI
Modification of the Terminal Residue of Apelin-13 Antagonizes Its Hypotensive Action
Dennis Lee,Victor Saldivia,Tuan V. Nguyen,Regina Cheng,Susan R. George,Susan R. George,Brian F. O'Dowd,Brian F. O'Dowd +7 more
TL;DR: It is shown that in native tissues preproapelin exists as a dimer, and the role of the carboxyl-terminal phenylalanine in the hypotensive action of apelin-13, analogs were generated and tested for their role on blood pressure regulation.
Journal ArticleDOI
Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19
Heng F Seow,Stefan Bröer,Angelika Bröer,Charles G. Bailey,Simon J Potter,Juleen A. Cavanaugh,John E.J. Rasko,John E.J. Rasko +7 more
TL;DR: The findings indicate that SLC6A19 is the long-sought gene that is mutated in Hartnup disorder; its identification provides the opportunity to examine the inconsistent multisystemic features of this disorder.
Journal ArticleDOI
Angiotensin-(1-7): Cardioprotective Effect in Myocardial Ischemia/Reperfusion
TL;DR: The results suggest that the antiarrhythmogenic effect of low concentrations of Ang-(1-7) is mediated by a specific receptor and that release of endogenous prostaglandins contributes to the alleviation of reversible and/or irreversible ischemia-reperfusion injury.
Journal ArticleDOI
Loss of Angiotensin-Converting Enzyme-2 (Ace2) Accelerates Diabetic Kidney Injury
Denise W. Wong,Gavin Y. Oudit,Heather N. Reich,Zamaneh Kassiri,Joyce Zhou,Qiao C. Liu,Peter H. Backx,Josef M. Penninger,Andrew M. Herzenberg,James W. Scholey +9 more
TL;DR: It is concluded that ACE2 plays a protective role in the diabetic kidney, and ACE2 is an important determinant of diabetic nephropathy.
Journal ArticleDOI
Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension.
Anderson J. Ferreira,Vinayak Shenoy,Yoriko Yamazato,Srinivas Sriramula,Joseph Francis,Lihui Yuan,Ronald K. Castellano,David A. Ostrov,Suk P. Oh,Michael J. Katovich,Mohan K. Raizada +10 more
TL;DR: Conceptual support is provided that activation of ACE2 by a small molecule can be a therapeutically relevant approach for treating and controlling PH.
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