Kosacka Joanna, Berger Claudia, Ceglarek Uta, Hoffmann Anne, Blüher Matthias, Klöting Nora
Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Liebigstr. 20, 04103 Leipzig, Germany.
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, Liebigstr. 21, 04103 Leipzig, Germany.
Metabolites. 2022 Mar 26;12(4):293. doi: 10.3390/metabo12040293.
The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is abundantly expressed in many organs. With respect to the role of circulating ACE2 and its receptor expression in the pathogenesis of the SARS-CoV-2 infection, it is still debated whether diseases such as hypertension or pharmacotherapies, including ACE inhibitors and angiotensin receptor blockers that affect ACE2 receptor expression, may modulate the severity and outcome of the coronavirus disease 2019 (COVID-19). We therefore tested the hypothesis that treatment with the ACE inhibitor Ramipril affects organ-specific ACE2 receptor mRNA and protein expression as well as the serum metabolome in BioBreeding (BB) rats. Twelve male BioBreeding rats were randomly divided into a Ramipril (10 mg/kg body weight) treatment group or a control group ( = 12; = 6 per group) over a period of seven days. Ramipril treatment resulted in the reduction of acylcarnitines (C3-C6) out of 64 metabolites. Among the different organs studied, only in the lungs did Ramipril treatment significantly increase both mRNA and ACE2 receptor membrane protein levels. Increased ACE2 receptor lung expression after Ramipril treatment was not associated with differences in ACE2 serum concentrations between experimental groups. Our data provide experimental in vivo evidence that the ACE inhibitor Ramipril selectively increases pulmonary ACE2 receptor mRNA and protein levels and reduces acylcarnitines.
血管紧张素转换酶2（ACE2）受体已被确定为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的进入受体，该受体在许多器官中大量表达。关于循环ACE2及其受体表达在SARS-CoV-2感染发病机制中的作用，诸如高血压等疾病或包括影响ACE2受体表达的ACE抑制剂和血管紧张素受体阻滞剂在内的药物疗法是否会调节2019冠状病毒病（COVID-19）的严重程度和结局仍存在争议。因此，我们检验了以下假设：在BioBreeding（BB）大鼠中，使用ACE抑制剂雷米普利治疗会影响器官特异性ACE2受体mRNA和蛋白表达以及血清代谢组。12只雄性BioBreeding大鼠在7天的时间内被随机分为雷米普利（10 mg/kg体重）治疗组或对照组（每组n = 12；每组n = 6）。雷米普利治疗导致64种代谢物中的酰基肉碱（C3 - C6）减少。在研究的不同器官中，只有肺部的雷米普利治疗显著增加了ACE2 mRNA和ACE2受体膜蛋白水平。雷米普利治疗后肺部ACE2受体表达增加与实验组之间ACE2血清浓度的差异无关。我们的数据提供了体内实验证据，表明ACE抑制剂雷米普利选择性增加肺部ACE2受体mRNA和蛋白水平并降低酰基肉碱。
