Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC.
Circ Res. 2023 May 12;132(10):1320-1337. doi: 10.1161/CIRCRESAHA.123.321883. Epub 2023 May 11.
The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection and viral replication. ACE2 is an important enzymatic component of the renin-angiotensin system (RAS) expressed in the lung and other organs. The peptidase regulates the levels of the peptide hormones Ang II and Ang-(1-7), which have distinct and opposing actions to one another, as well as other cardiovascular peptides. A potential consequence of severe acute respiratory syndrome-related coronavirus-2 infection is reduced ACE2 activity by internalization of the viral-ACE2 complex and subsequent activation of the RAS (higher ratio of Ang II:Ang-[1-7]) that may exacerbate the acute inflammatory events in COVID-19 patients and possibly contribute to the effects of long COVID-19. Moreover, COVID-19 patients present with an array of autoantibodies to various components of the RAS including the peptide Ang II, the enzyme ACE2, and the AT AT and Mas receptors. Greater disease severity is also evident in male COVID-19 patients, which may reflect underlying sex differences in the regulation of the 2 distinct functional arms of the RAS. The current review provides a critical evaluation of the evidence for an activated RAS in COVID-19 subjects and whether this system contributes to the greater severity of severe acute respiratory syndrome-related coronavirus-2 infection in males as compared with females.
当前的冠状病毒病（COVID-19）疫情导致了巨大的健康负担，成为美国第三大死亡原因，并可能导致预期寿命下降。与严重急性呼吸系统综合征相关的冠状病毒-2 与表面结合的肽酶血管紧张素转换酶 2（ACE2，EC 3.4.17.23）结合，导致组织感染和病毒复制。ACE2 是肺和其他器官中肾素-血管紧张素系统（RAS）的重要酶组成部分。该肽酶调节肽激素 Ang II 和 Ang-（1-7）的水平，它们彼此具有不同且相反的作用，以及其他心血管肽。严重急性呼吸系统综合征相关冠状病毒-2 感染的潜在后果是通过病毒-ACE2 复合物的内化和随后的 RAS 激活（Ang II：Ang-（1-7）的比值更高）导致 ACE2 活性降低，这可能会加剧 COVID-19 患者的急性炎症事件，并可能导致长 COVID-19 的影响。此外，COVID-19 患者表现出针对 RAS 多种成分的自身抗体，包括肽 Ang II、酶 ACE2 以及 AT1 和 Mas 受体。男性 COVID-19 患者的疾病严重程度也更为明显，这可能反映了 RAS 两个不同功能臂的调节中存在潜在的性别差异。目前的综述对 RAS 在 COVID-19 患者中被激活的证据进行了批判性评估，以及该系统是否导致男性严重急性呼吸系统综合征相关冠状病毒-2 感染的严重程度大于女性。
