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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Journal ArticleDOI
SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway
TL;DR: It is found that SARS-CoV enters cells via pH- and receptor-dependent endocytosis, and this finding contributes to the understanding of SARS -CoV pathogenesis, providing new information for anti-viral drug research.
Journal ArticleDOI
The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism.
Kazuhiko Tatemoto,Kiyoshige Takayama,Min-Xu Zou,Iku Kumaki,Wei Zhang,Kimitsuka Kumano,Mineko Fujimiya +6 more
TL;DR: It was found that mean arterial pressure after the administration of apelin, apelin-13, andapelin-36 at a dose of 10 nmol/kg in anaesthetized rats was reduced by 26+/-5, 11+/-4, and 5-/-4 mm Hg, respectively, suggesting that apelin may lower blood pressure via a nitric oxide-dependent mechanism.
Journal ArticleDOI
ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.
Paul Towler,Bart L. Staker,Sridhar Prasad,Saurabh Menon,Jin Tang,Thomas F. Parsons,Dominic Ryan,Martin Fisher,David Williams,Natalie A. Dales,Michael A. Patane,Michael W. Pantoliano +11 more
TL;DR: The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence that offers insights regarding the action of residues involved in catalysis and substrate specificity.
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Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry
Shiori Haga,Norio Yamamoto,Chikako Nakai-Murakami,Yoshiaki Osawa,Kenzo Tokunaga,Tetsutaro Sata,Naoki Yamamoto,Takehiko Sasazuki,Yukihito Ishizaka +8 more
TL;DR: It is found that the spike protein of SARS-CoV (SARS-S) induced TNF-α-converting enzyme (TACE)-dependent shedding of the ACE2 ectodomain, and this data suggest that cellular signals triggered by the interaction of Sars- coV with ACE2 are positively involved in viral entry but lead to tissue damage.
Journal ArticleDOI
Pathophysiology of acute lung injury and the acute respiratory distress syndrome.
TL;DR: This review summarizes the current understanding of the pathophysiology of what is now termed the acute respiratory distress syndrome and its less severe form acute lung injury, with an emphasis on cellular and molecular mechanisms of injury that may represent potential therapeutic targets.
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