From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands (A.H.J.D.).
Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, FL (M.E.).
Hypertension. 2020 Jun;75(6):1382-1385. doi: 10.1161/HYPERTENSIONAHA.120.15082. Epub 2020 Mar 25.
During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.
在严重急性呼吸综合征冠状病毒 2 传播期间，一些仍在出现且需要全面分析的数据报告表明，某些患者群体有患 COVID-19 的风险。这包括患有高血压、心脏病、糖尿病的患者，以及显然的老年人。许多这些患者都接受肾素-血管紧张素系统阻滞剂的治疗。由于 ACE2（血管紧张素转换酶 2）蛋白是促进冠状病毒进入细胞的受体，因此人们普遍认为，使用肾素-血管紧张素系统阻滞剂可能会增加发生严重和致命的严重急性呼吸综合征冠状病毒 2 感染的风险。本文讨论了这一概念。全长形式的 ACE2 是一种膜结合酶，而其较短的（可溶性）形式则以非常低的水平在血液中循环。作为单羧肽酶，ACE2 有助于降解包括血管紧张素 I 和 II 在内的几种底物。ACE（血管紧张素转换酶）抑制剂不抑制 ACE2，因为 ACE 和 ACE2 是不同的酶。尽管已经证明血管紧张素 II 型 1 受体阻滞剂可在实验动物中上调 ACE2，但证据并不总是一致，并且在不同的血管紧张素 II 型 1 受体阻滞剂和不同的器官中存在差异。此外，没有数据支持 ACE 抑制剂或血管紧张素 II 型 1 受体阻滞剂给药通过增加 ACE2 表达来促进冠状病毒进入动物或人类的观点。事实上，动物数据支持 ACE2 表达升高可提供潜在的保护肺和心血管作用。总之，根据目前的可用证据，不应因担心冠状病毒感染而停止使用肾素-血管紧张素系统阻滞剂的治疗。
