The Impact of Angiotensin Converting Enzyme Inhibition and/or Angiotensin Receptor Blockade on Tissue Expression of the SARS‐CoV‐2 Receptor ACE2 in Mice

• DOI: 10.1096/fasebj.2021.35.s1.04584
• Publication Date: 2021-06-11T01:05:27Z
• Authors: Aline Silva Moreira; Steven Brooks; Rachel Smith; Ian Moore; Hans Ackerman
• Keywords: Telmisartan; Angiotensin-converting enzyme 2; Receptor expression

The angiotensin-converting enzyme 2 (ACE2) is an established receptor and entry point for the novel SARS-CoV-2 coronavirus, as spike protein on viral envelope binds ACE2 receptor. Published histological profiling revealed to be highly expressed human lung alveolar epithelial cells enterocytes of small intestine, well arterial venous endothelial cells. Given widespread abundance across tissues, there has been much speculation regarding whether ACE inhibitors (ACEi) and/or Angiotensin Receptor Blockers (ARB) might alter tissue expression thereby change risk transmission or development severe complications. Therefore, aim this ongoing study measure impact ACEi ARB singly in combination versus placebo control distribution male female mice. A factorial design was employed with following exposures: (lisinopril, 10 mg/kg/day), (losartan, both drugs, water control. Drugs were delivered via drinking water. C57BL/6J Mice 8 weeks age at start experiment. After 21 days treatment, four mice (two males two females) from each treatment group euthanized, followed by perfusion collection. 12 more untreated combined increase sample size reference 16 (8 males, females). brain, kidney, liver, lung, intestine measured ELISA (Abcam) normalized BCA-measured total protein. Two-way ANOVA performed test differences levels organ sex among mice; Mann-Whitney tests compare drug group. Among mice, differed (p < 0.01), but no between females a given = 0.20). Males subsequent analyses. ACEi, ARB, therapy lowered compared brain (ACEi p 0.04; ACEi+ARB kidney 0.03; 0.02; 0.02), 0.01; 0.01). not therapy, liver 0.02). None treatments changed intestine. These results indicate that reduces ACE2, receptor, key tissues affected virus, including brain. An validation will evaluate gene earlier time points, after discontinuation treatment. provide valuable insight into potential benefit starting stopping during COVID-19 pandemic.