SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex.

Autor:	Ensor CM; Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536., AlSiraj Y; Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536., Shoemaker R; Department of Dietetics and Human Nutrition, College of Food, Agriculture and the Environment, University of Kentucky, Lexington, KY 40536., Sturgill J; Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536., Keshavamurthy S; Division of Cardiothoracic Surgery, Department of Surgery, College of Medicine, University of Kentucky, Lexington, KY 40536., Gordon EM; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536., Dong BE; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536., Waters C; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536., Cassis LA; Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2021 Sep 14. Date of Electronic Publication: 2021 Sep 14.
DOI:	10.1101/2021.09.14.460275
Abstrakt:	Angiotensin converting enzyme 2 (ACE2) is an enzyme that limits activity of the renin-angiotensin system (RAS) and also serves as a receptor for the SARS-CoV-2 Spike (S) protein. Binding of S protein to ACE2 causes internalization which activates local RAS. ACE2 is on the X chromosome and its expression is regulated by sex hormones. In this study, we defined ACE2 mRNA abundance and examined effects of S protein on ACE2 activity and/or angiotensin II (AngII) levels in pivotal tissues (lung, adipose) from male and female mice. In lung, ACE2 mRNA abundance was reduced following gonadectomy (GDX) of male and female mice and was higher in XX than XY mice of the Four Core Genotypes (FCG). Reductions in lung ACE2 mRNA abundance by GDX occurred in XX, but not XY FCG female mice. Lung mRNA abundance of ADAM17 and TMPRSS2, enzymes that shed cell surface ACE2 and facilitate viral cell entry, was reduced by GDX in male but not female mice. For comparison, adipose ACE2 mRNA abundance was higher in female than male mice and higher in XX than XY FCG mice. Adipose ADAM17 mRNA abundance was increased by GDX of male and female mice. S protein reduced ACE2 activity in alveolar type II epithelial cells and 3T3-L1 adipocytes. Administration of S protein to male and female mice increased lung AngII levels and decreased adipose ACE2 activity in male but not female mice. These results demonstrate that sex differences in ACE2 expression levels may impact local RAS following S protein exposures. Competing Interests: Disclosures No conflicts of interest, financial or otherwise, are declared by the authors.
Databáze:	MEDLINE
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