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
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Journal ArticleDOI
Decreased glomerular and tubular expression of ACE2 in patients with type 2 diabetes and kidney disease
TL;DR: The results suggest that the kidney disease of patients with type 2 diabetes is associated with a reduction in ACE2 gene and protein expression and this may contribute to the progression of renal injury.
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Regulation of ACE2 in cardiac myocytes and fibroblasts.
TL;DR: The results indicate that multiple hypertrophic and anti-hypertropic peptides regulate ACE2 production in myocytes, suggesting that ACE2 expression in the heart is dependent upon the compliment and concentration of regulatory molecules.
Journal ArticleDOI
ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice.
TL;DR: It is shown that chronic pharmacologic ACE2 inhibition worsens glomerular injury in streptozotocin-induced diabetic mice in association with increased ACE expression.
Journal ArticleDOI
Essential role for collectrin in renal amino acid transport
Ursula Danilczyk,Renu Sarao,Christine Remy,Chahira Benabbas,Gerti Stange,Andreas Richter,Sudha Arya,J. Andrew Pospisilik,Dustin Singer,Simone M. R. Camargo,Victoria Makrides,Tamara Ramadan,François Verrey,Carsten A. Wagner,Josef M. Penninger +14 more
TL;DR: It is reported that targeted disruption of collectrin in mice results in a severe defect in renal amino acid uptake owing to downregulation of apical amino acid transporters in the kidney.
Journal ArticleDOI
Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls.
Sonoo Mizuiri,Hiromichi Hemmi,Michitsune Arita,Yasushi Ohashi,Yoshihide Tanaka,Moriatsu Miyagi,Ken Sakai,Yukio Ishikawa,Kazutoshi Shibuya,Hiroki Hase,Atsushi Aikawa +10 more
TL;DR: The high ACE/ACE2 ratio in kidneys of patients with type 2 diabetes with overt nephropathy may contribute to renal injury.
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