Wu Congqing, Ye Dien, Mullick Adam E, Li Zhenyu, Danser A H Jan, Daugherty Alan, Lu Hong S
bioRxiv. 2020 Jun 18:2020.06.08.137331. doi: 10.1101/2020.06.08.137331.
Angiotensin-converting enzyme 2 (ACE2), a component of the renin-angiotensin system, is a receptor for SARS-CoV-2, the virus that causes COVID-19. To determine whether the renin-angiotensin inhibition regulates ACE2 expression, either enalapril (an angiotensin-converting enzyme inhibitor) or losartan (an AT1 receptor blocker) was infused subcutaneously to male C57BL/6J mice for two weeks. Neither enalapril nor losartan changed abundance of ACE2 mRNA in lung, ileum, kidney, and heart. Viral entry also depends on transmembrane protease serine 2 (TMPRSS2) to prime the S protein. TMPRSS2 mRNA was abundant in lungs and ileum, modest in kidney, but barely detectable in heart. TMPRSS2 mRNA abundance was not altered by either enalapril or losartan in any of the 4 tissues. Next, we determined whether depletion of angiotensinogen (AGT), the unique substrate of the renin-angiotensin system, changes ACE2 and TMPRSS2 mRNA abundance. AGT antisense oligonucleotides (ASO) were injected subcutaneously to male C57BL/6J mice for 3 weeks. Abundance of ACE2 mRNA was unchanged in any of the 4 tissues, but TMPRSS2 mRNA was significantly decreased in lungs. Our data support that the renin-angiotensin inhibition does not regulate ACE2 and hence are not likely to increase risk for COVID-19.
血管紧张素转换酶2（ACE2）是肾素-血管紧张素系统的一个组成部分，是引发新冠肺炎的SARS-CoV-2病毒的受体。为了确定肾素-血管紧张素抑制是否调节ACE2表达，将依那普利（一种血管紧张素转换酶抑制剂）或氯沙坦（一种AT1受体阻滞剂）皮下注射给雄性C57BL/6J小鼠，持续两周。依那普利和氯沙坦均未改变肺、回肠、肾脏和心脏中ACE2 mRNA的丰度。病毒进入还依赖跨膜蛋白酶丝氨酸2（TMPRSS2）来激活S蛋白。TMPRSS2 mRNA在肺和回肠中丰富，在肾脏中适中，但在心脏中几乎检测不到。依那普利或氯沙坦均未改变这4个组织中任何一个组织的TMPRSS2 mRNA丰度。接下来，我们确定肾素-血管紧张素系统的唯一底物血管紧张素原（AGT）的耗竭是否会改变ACE2和TMPRSS2 mRNA的丰度。将AGT反义寡核苷酸（ASO）皮下注射给雄性C57BL/6J小鼠，持续3周。4个组织中任何一个组织的ACE2 mRNA丰度均未改变，但肺中的TMPRSS2 mRNA显著降低。我们的数据支持肾素-血管紧张素抑制不调节ACE2，因此不太可能增加感染新冠肺炎的风险。
