Triposkiadis Filippos, Xanthopoulos Andrew, Giamouzis Grigorios, Boudoulas Konstantinos Dean, Starling Randall C, Skoularigis John, Boudoulas Harisios, Iliodromitis Efstathios
Department of Cardiology, Larissa University General Hospital, 41110 Larissa, Greece.
Department of Medicine/Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA.
J Clin Med. 2021 Aug 29;10(17):3885. doi: 10.3390/jcm10173885.
Angiotensin (ANG)-converting enzyme (ACE2) is an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). ACE2 also contributes to a deviation of the lung renin-angiotensin system (RAS) towards its counter-regulatory axis, thus transforming harmful ANG II to protective ANG (1-7). Based on this purported ACE2 double function, it has been put forward that the benefit from ACE2 upregulation with renin-angiotensin-aldosterone system inhibitors (RAASi) counterbalances COVID-19 risks due to counter-regulatory RAS axis amplification. In this manuscript we discuss the relationship between ACE2 expression and function in the lungs and other organs and COVID-19 severity. Recent data suggested that the involvement of ACE2 in the lung counter-regulatory RAS axis is limited. In this setting, an augmentation of ACE2 expression and/or a dissociation of ACE2 from the ANG (1-7)/Mas pathways that leaves unopposed the ACE2 function, the SARS-CoV-2 entry receptor, predisposes to more severe disease and it appears to often occur in the relevant risk factors. Further, the effect of RAASi on ACE2 expression and on COVID-19 severity and the overall clinical implications are discussed.
血管紧张素（ANG）转换酶2（ACE2）是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的一种进入受体，该病毒可导致2019冠状病毒病（COVID-19）。ACE2还促使肺肾素-血管紧张素系统（RAS）向其反调节轴偏移，从而将有害的血管紧张素II转化为具有保护作用的血管紧张素（1-7）。基于这种所谓的ACE2双重功能，有人提出，肾素-血管紧张素-醛固酮系统抑制剂（RAASi）上调ACE2带来的益处可抵消因反调节RAS轴放大导致的COVID-19风险。在本手稿中，我们讨论了肺及其他器官中ACE2的表达和功能与COVID-19严重程度之间的关系。最近的数据表明，ACE2在肺反调节RAS轴中的作用有限。在这种情况下，ACE2表达的增加和/或ACE2与血管紧张素（1-7）/Mas通路的解离，使得ACE2功能（SARS-CoV-2进入受体）不受抑制，易导致更严重的疾病，且这似乎经常发生在相关风险因素中。此外，还讨论了RAASi对ACE2表达、COVID-19严重程度的影响以及总体临床意义。
