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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Jing-Wei Bian,Zi-Jian Li +1 more
TL;DR: An in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma of how to limit virus entry but protect ACE2 physiological functions.
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COVID-19 and RAS: Unravelling an Unclear Relationship.
Damiano D'Ardes,Andrea Boccatonda,Ilaria Rossi,Maria Teresa Guagnano,Francesca Santilli,Francesco Cipollone,M. Bucci +6 more
TL;DR: The renin-angiotensin system plays a main role in regulating blood pressure and electrolyte and liquid balance, and previous evidence suggests that RAS may represent an important target for the treatment of lung pathologies.
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ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives
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TL;DR: An overview of the state-of-the-art knowledge on ACE2 biochemistry and pathophysiology is presented, outlining open issues in the context of COVID-19 disease and potential experimental and clinical developments.
References
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Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.
Wenhui Li,Michael Moore,Natalya Vasilieva,Jianhua Sui,Swee Kee Wong,Michael A. Berne,Mohan Somasundaran,John L. Sullivan,Katherine Luzuriaga,Thomas C. Greenough,Hyeryun Choe,Michael Farzan +11 more
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TL;DR: A molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses is provided.
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A Novel Angiotensin-Converting Enzyme–Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9
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TL;DR: The organ- and cell-specific expression of ACE2 and its unique cleavage of key vasoactive peptides suggest an essential role for ACE2 in the local renin-angiotensin system of the heart and kidney.
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TL;DR: Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closelyrelated to any of the previouslycharacterized coronaviruses.
Journal ArticleDOI
Angiotensin-converting enzyme 2 protects from severe acute lung failure
Yumiko Imai,Keiji Kuba,Shuan Rao,Yi Huan,Feng Guo,Bin Guan,Peng Yang,Renu Sarao,Teiji Wada,Howard Leong-Poi,Michael A. Crackower,Akiyoshi Fukamizu,Chi-chung Hui,Lutz Hein,Stefan Uhlig,Arthur S. Slutsky,Chengyu Jiang,Josef M. Penninger +17 more
TL;DR: It is reported that ACE2 and the angiotensin II type 2 receptor (AT2) protect mice from severe acute lung injury induced by acid aspiration or sepsis, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.
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