ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.

中文翻译：

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血管紧张素转换酶 2：肾素-血管紧张素系统的 SARS-CoV-2 受体和调节器：庆祝 ACE2 发现 20 周年。

ACE2（血管紧张素转换酶 2）围绕其三价功能具有多种生理作用：肾素-血管紧张素系统的负调节剂、氨基酸转运的促进剂和严重急性呼吸综合征冠状病毒 (SARS-CoV)和 SARS-CoV-2 受体。ACE2广泛表达，包括肺、心血管系统、肠道、肾脏、中枢神经系统和脂肪组织。ACE2 最近被确定为 SARS-CoV-2 受体，是导致 2019 年冠状病毒病的感染因子，在免疫、炎症、ACE2 和心血管疾病之间提供了关键联系。尽管与 SARS-CoV 具有密切的进化关系，但 SARS-CoV-2 的受体结合域在几个关键氨基酸残基上存在差异，从而与人类 ACE2 受体具有更强的结合亲和力，这可能是 SARS 具有更强致病性的原因-CoV-2。与 SARS-CoV-2 结合后 ACE2 功能丧失是由内吞作用以及蛋白水解裂解和加工的激活驱动的。ACE2系统是对抗射血分数降低和保留的心力衰竭（包括心肌梗死和高血压）以及肺部疾病和糖尿病的关键保护途径。ACE2 对肠道生态失调和血管通透性的控制已成为肺动脉高压和糖尿病心血管并发症的重要机制。重组 ACE2、Ace2、Ang 1-7 类似物和 Mas 受体激动剂的基因传递可增强 ACE2 作用，并可作为与激活的肾素-血管紧张素系统相关的疾病的潜在疗法。rhACE2（重组人ACE2）已完成临床试验，并分别有效降低或升高血浆血管紧张素II和血管紧张素1-7水平。我们的综述总结了过去 20 年的进展，强调了 ACE2 作为新型 SARS-CoV-2 受体和肾素-血管紧张素系统负调节因子的关键作用，以及对 2019 年冠状病毒病大流行和相关心血管疾病的影响疾病。