SARS-CoV-2 与 ACE2：解决 ARB 和 ACEI 争议的生物学和临床数据。
SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy.
机构信息
Heart, Vascular and Thoracic Institute, United States; Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
出版信息
EBioMedicine. 2020 Aug;58:102907. doi: 10.1016/j.ebiom.2020.102907. Epub 2020 Aug 6.
BACKGROUND
SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful.
METHODS
Animal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed.
FINDINGS AND INTERPRETATION
SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets.
背景
SARS-CoV-2 通过其刺突蛋白与血管紧张素转换酶 2（ACE2）结合进入细胞。在动物模型中，血管紧张素转换酶抑制剂（ACEI）或血管紧张素 II 受体阻滞剂（ARB）被报道会增加 ACE2 的表达，而在伴有这些药物共同治疗的合并症的患者中报告了更差的结局，这导致了在 COVID-19 大流行期间关于这些药物是否可能有益或有害的争议。
方法
对与肾素-血管紧张素系统（RAS）的生物学、它与激肽释放酶-激肽系统（KKS）和 SARS-CoV-2 的相互作用以及临床研究相关的动物、体外和临床数据进行了综述。
结果和解释
SARS-CoV-2 劫持 ACE2 入侵和损害细胞，下调 ACE2，降低其保护作用并加剧有害的 Ang II 作用。然而，回顾性观察性研究并未显示 ACEI 或 ARB 使用的感染风险更高。尽管如此，在冠状病毒感染的情况下对 RAS 和 KKS 的研究可能会产生治疗靶点。
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