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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Glomerular Localization and Expression of Angiotensin-Converting Enzyme 2 and Angiotensin-Converting Enzyme: Implications for Albuminuria in Diabetes
TL;DR: The finding that chronic ACE2 inhibition increases UAE suggests that ACE2, likely by modulating the levels of glomerular angiotensin II via its degradation, may be a target for therapeutic interventions that aim to reduce albuminuria and glomersular injury.
Journal ArticleDOI
Immunopathogenesis of coronavirus infections: implications for SARS
Stanley Perlman,Ajai A. Dandekar +1 more
TL;DR: Studies of animals that are infected with other coronaviruses indicate that excessive and sometimes dysregulated responses by macrophages and other pro-inflammatory cells might be particularly important in the pathogenesis of disease that is caused by infection with these viruses.
Journal ArticleDOI
Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome.
Richard P. Marshall,Suzanne Webb,G Bellingan,Hugh Montgomery,Babar Chaudhari,Robin J. McAnulty,Steve E. Humphries,Michael Hill,Geoffrey J. Laurent +8 more
TL;DR: A potential role for renin-angiotensin systems in the pathogenesis of ARDS is suggested and for the first time genetic factors in the development and progression of this syndrome are implicate.
Journal ArticleDOI
Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo
Junji Ishida,Tatsuo Hashimoto,Tatsuo Hashimoto,Yasumi Hashimoto,Shiro Nishiwaki,Taku Iguchi,Shuichi Harada,Takeshi Sugaya,Hitomi Matsuzaki,Rie Yamamoto,Naotaka Shiota,Hideki Okunishi,Minoru Kihara,Satoshi Umemura,Fumihiro Sugiyama,Ken-ichi Yagami,Yoshitoshi Kasuya,Naoki Mochizuki,Akiyoshi Fukamizu +18 more
TL;DR: It is demonstrated that APJ exerts the hypotensive effect in vivo and plays a counterregulatory role against the pressor action of angiotensin II.
Journal ArticleDOI
Trilogy of ACE2: a peptidase in the renin-angiotensin system, a SARS receptor, and a partner for amino acid transporters.
TL;DR: The multiple biological functions of ACE2 are discussed and it is shown that both ACE2 and its homologue Collectrin can associate with amino acid transporters and play essential role in the absorption of amino acids in the kidney and gut.
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