Leowattana Wattana, Leowattana Tawithep, Leowattana Pathomthep
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Bangkok, Thailand.
Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Bangkok, Thailand.
World J Clin Cases. 2022 Dec 6;10(34):12470-12483. doi: 10.12998/wjcc.v10.i34.12470.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.
自2019年12月以来，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发了广泛的疫情。世界卫生组织将与SARS-CoV-2感染相关的疾病称为2019冠状病毒病（COVID-19）。无症状和亚临床感染、严重的高炎症状态以及死亡率都是临床症状的例子。SARS-CoV-2病毒在附着于血管紧张素转换酶2（ACE2）受体后，可通过膜融合和内吞作用进入细胞。SARS-CoV-2的刺突蛋白（S蛋白）与ACE2之间的连接不仅能使病毒附着于靶细胞，还可能损害ACE2的功能。ACE2可催化活性血管收缩剂八肽血管紧张素（Ang）II水解为七肽Ang-(1-7)和游离L-苯丙氨酸，从而控制血压。此外，ACE2可将Ang I分解为Ang-(1-9)并代谢为Ang-(1-7)。大量研究表明，循环中的ACE2（cACE2）和Ang-(1-7)能够修复多种心血管疾病中的心肌损伤，并具有抗炎、抗氧化、抗凋亡和抗心肌细胞纤维化作用。已有一些关于提高COVID-19患者ACE2表达的建议，这可能作为开发新型治疗方法的靶点。就此而言，可溶性重组人ACE2（hrsACE2）可中和SARS-CoV-2，它与病毒S蛋白结合，通过降低Ang II浓度并增强向Ang-(1-7)的转化，减少包括心脏、肾脏和肺在内的多种器官的损伤。本综述旨在研究SARS-CoV-2与cACE2之间的关系。此外，还将讨论一些潜在的治疗方法，以促使ACE/ACE-2平衡向有利于ACE-2/Ang-(1-7)轴的方向倾斜。
