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bioRxiv · 10.1101/2020.06.08.137331

Effects of Renin-Angiotensin Inhibition on ACE2 and TMPRSS2 Expression

Wu, C.·Ye, D.·Mullick, A. E.·Li, Z.·Daugherty, A.·Lu, H. S.
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Abstract

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.

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Wu, C., Ye, D., Mullick, A. E., Li, Z., Daugherty, A., Lu, H. S.. 2020-06-08. Effects of Renin-Angiotensin Inhibition on ACE2 and TMPRSS2 Expression. https://doi.org/10.1101/2020.06.08.137331

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