当前位置: X-MOL 学术bioRxiv. Physiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Kidney and Lung ACE2 expression after an ACE inhibitor or an Ang II receptor blocker: implications for COVID-19
bioRxiv - Physiology Pub Date : 2020-05-20 , DOI: 10.1101/2020.05.20.106658
Jan Wysocki , Enrique Lores , Minghao Ye , Maria Jose Soler , Daniel Batlle

Background: There have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in ACE2, the main receptor for SARs-CoV-2. Methods: Kidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes. Results: In a global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0.05. In ACE 8/8 mice that over-expresses cardiac ACE protein but also has no kidney ACE expression, ACE2 protein in kidney membranes was also decreased (38 % of the WT, p<0.01). In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein (37% in captopril treated p<0.01) and 76% in telmisartan treated p <0.05). In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control ) or telmisartan (93% of control). Conclusions: Genetic kidney ACE protein deficiency, suppressed enzymatic activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 in kidney membranes. ACE2 protein in kidney or lungs is decreased or unaffected by RAS blockers indicating that these medications can not pose a risk for SARS-CoV-2 infection related to amplification of ACE2 at these two target sites for viral entry.

中文翻译:

ACE抑制剂或Ang II受体阻滞剂后肾脏和肺ACE2的表达:对COVID-19的影响

背景:人们一直担心ACE抑制剂和Ang II受体阻滞剂可能会导致SAR2-CoV-2的主要受体ACE2增加。方法:采用两种肾脏ACE消融基因模型的肾脏以及卡托普利或替米沙坦治疗的小鼠,检查分离的肾脏和肺膜中的ACE2。结果:在全球性的ACE KO小鼠中,肾膜中的ACE2蛋白丰度降低至野生型的42%,p <0.05。在过度表达心脏ACE蛋白但也没有肾脏ACE表达的ACE 8/8小鼠中,肾膜中的ACE2蛋白也降低了(WT的38%,p <0.01)。在接受卡托普利或替米沙坦治疗2周的小鼠的肾膜中,ACE2蛋白降低(卡托普利治疗37%,p <0.01)和替米沙坦治疗76%,p <0.05)。在肺膜中,ACE2的表达非常低,无法通过蛋白质印迹法检测到,但是在用卡托普利(对照组为118%)或替米沙坦(对照组为93%)治疗的小鼠中,未检测到ACE2活性的显着差异。结论:遗传性肾脏ACE蛋白缺乏,卡托普利抑制酶活性或替米沙坦阻断AT1受体均与肾膜ACE2减少有关。RAS阻断剂可减少或不受肾脏或肺中ACE2蛋白的影响,这表明这些药物不会对与这两个病毒进入靶位点ACE2扩增有关的SARS-CoV-2感染构成风险。
更新日期:2020-05-20
down
wechat
bug