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.
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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.
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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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Overexpression of Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Causes Long-Term Decrease in Blood Pressure in the Spontaneously Hypertensive Rats
TL;DR: Observations demonstrate that overexpression of ACE2 overcomes its intrinsic decrease in the RVLM and decreases high blood pressure in the spontaneously hypertensive rat.
Journal ArticleDOI
ACE2 Deficiency Modifies Renoprotection Afforded by ACE Inhibition in Experimental Diabetes
Chris Tikellis,Katarzyna Bialkowski,Josepha Pete,Karen Sheehy,Qui Su,Colin I. Johnston,Mark E. Cooper,Merlin C. Thomas +7 more
TL;DR: The expression of ACE2 is significantly modified by diabetes, which impacts both pathogenesis of kidney disease and responsiveness to RAS blockade, and data indicate thatACE2 is a complex and site-specific modulator of diabetic kidney disease.
Journal ArticleDOI
Transgenic Angiotensin-Converting Enzyme 2 Overexpression in Vessels of SHRSP Rats Reduces Blood Pressure and Improves Endothelial Function
Brit Rentzsch,Mihail Todiras,Radu Iliescu,Elena Popova,Luciana Aparecida Campos,Marilene L. Oliveira,Ovidiu Baltatu,Robson A.S. Santos,Michael Bader +8 more
TL;DR: Data demonstrate that vascular ACE2 overexpression in SHRSP reduces hypertension probably by locally degrading angiotensin II and improving endothelial function, suggesting activation of the ACE2/angiotens in-(1-7) axis may be a novel therapeutic strategy in hypertension.
Journal ArticleDOI
The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation
Kenji Fukui,Qin Yang,Yang Cao,Noriko Takahashi,Hiroyasu Hatakeyama,Haiyan Wang,Jun Wada,Yanling Zhang,Lorella Marselli,Takao Nammo,Kazue Yoneda,Mineki Onishi,Shigeki Higashiyama,Yuji Matsuzawa,Frank J. Gonzalez,Gordon C. Weir,Haruo Kasai,Iichiro Shimomura,Jun-ichiro Miyagawa,Claes B. Wollheim,Kazuya Yamagata +20 more
TL;DR: It is reported that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells and is a regulator of SNARE complex function, which thereby controls insulin exocytosis.
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Tmem27: a cleaved and shed plasma membrane protein that stimulates pancreatic beta cell proliferation.
TL;DR: The results identify a pancreatic beta cell transmembrane protein that regulates cell growth of pancreatic islets and transgenic mice with increased expression of Tmem27 in pancreaticbeta cells exhibit increased beta cell mass.
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