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Multiple Functions of Angiotensin-Converting Enzyme 2 and Its Relevance in Cardiovascular Diseases

机译:血管紧张素转换酶2的多功能及其在心血管疾病中的相关性

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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.??(Circ J?2013; 77: 301–308)
机译:血管紧张素转换酶2(ACE2)是肾素-血管紧张素系统的负调节剂,并起着重要的SARS冠状病毒受体和中性氨基酸转运蛋白稳定剂的作用。 ACE2催化血管紧张素II向血管紧张素1-7的转化,从而平衡ACE活性。越来越多的证据表明,ACE2的酶活性在心血管疾病中具有保护作用。 ACE2的损失可能是有害的,因为它会导致心脏功能恶化以及心脏,肾脏和血管病变。已证明重组可溶性人ACE2蛋白在包括心血管疾病在内的各种动物模型中均显示出有益的作用。 ACE2是一种多功能酶,因此可能作用于其他血管活性肽,例如Apelin,Apelin是血压和心肌收缩力的重要调节剂。此外,ACE2在结构上是一种嵌合蛋白,它是从2个基因的重复中出现的:在羧肽酶结构域与ACE的同源性和在跨膜C末端结构域与Collectrin的同源性。 ACE2已与Hartnup病(一种氨基酸稳态疾病)有关,并且通过其在氨基酸转运中的功能,最近发现ACE2可控制肠道炎症和腹泻,从而调节肠道微生物组。这篇综述总结并讨论了ACE2的结构和多种功能,以及该关键酶在疾病发病机理中的相关性。(Circ J?2013; 77:301-308)

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