Alabsi Sarah, Dhole Atharva, Hozayen Sameh, Chapman Scott A
University of Minnesota School of Medicine, 420 Delaware St. SE, Minneapolis, MN 55455, USA.
Department of Internal Medicine, University of Minnesota, 420 Delaware St. SE, Minneapolis, MN 55455, USA.
Microorganisms. 2023 Feb 28;11(3):612. doi: 10.3390/microorganisms11030612.
Angiotensin-converting enzyme 2 (ACE2), first discovered in 2000, serves as an important counterregulatory enzyme to the angiotensin II-mediated vasoconstrictive, pro-inflammatory, and pro-fibrotic actions of the renin-angiotensin system (RAS). Conversion of angiotensin II to the peptide angiotensin 1-7 (ANG 1-7) exerts protective vasodilatory, anti-inflammatory, and anti-fibrotic actions through interaction with the MasR receptor. There are many important considerations when noting the role of ACE2 in the pathogenesis and sequelae of COVID-19 infection. ACE2, in the role of COVID-19 infection, was recognized early in 2020 at the beginning of the pandemic as a cell membrane-bound and soluble binding site for the viral spike protein facilitating entering into tissue cells expressing ACE2, such as the lungs, heart, gut, and kidneys. Mechanisms exist that alter the magnitude of circulating and membrane-bound ACE2 (e.g., SARS-CoV-2 infection, viral variants, patient characteristics, chronic disease states, and the degree of cell surface expression of ACE2) and the influence these mechanisms have on the severity of disease and associated complications (e.g., respiratory failure, systemic inflammatory response syndrome, acute myocarditis, acute kidney injury). Several medications alter the ACE2 receptor expression, but whether these medications can influence the course of the disease and improve outcomes is unclear. In this review, we will discuss what is known about the interrelation of SARS-CoV-2, ACE2 and the factors that may contribute to the variability of its expression and potential contributors to the severity of COVID-19 infection.
血管紧张素转换酶2（ACE2）于2000年首次被发现，是肾素-血管紧张素系统（RAS）中血管紧张素II介导的血管收缩、促炎和促纤维化作用的重要负调节酶。血管紧张素II转化为肽血管紧张素1-7（ANG 1-7）通过与MasR受体相互作用发挥保护性血管舒张、抗炎和抗纤维化作用。在关注ACE2在COVID-19感染的发病机制和后遗症中的作用时，有许多重要的考虑因素。在2020年疫情开始时，ACE2在COVID-19感染中的作用就被认识到，它是病毒刺突蛋白的细胞膜结合和可溶性结合位点，有助于病毒进入表达ACE2的组织细胞，如肺、心脏、肠道和肾脏。存在一些机制可改变循环和膜结合ACE2的水平（例如，SARS-CoV-2感染、病毒变体、患者特征、慢性疾病状态以及ACE2的细胞表面表达程度），以及这些机制对疾病严重程度和相关并发症（例如，呼吸衰竭、全身炎症反应综合征、急性心肌炎、急性肾损伤）的影响。几种药物可改变ACE2受体表达，但这些药物是否能影响疾病进程并改善预后尚不清楚。在本综述中，我们将讨论关于SARS-CoV-2、ACE2之间的相互关系，以及可能导致其表达变异的因素和COVID-19感染严重程度的潜在影响因素。
