Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia–reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and higher expression of both ACE-2 and TMPRSS-2 was observed for lung alveoli and bronchioli, kidney tubules, and liver sinusoids. Our experimental data indicate that gonadal hormones and biological sex do not alter ACE-2 and TMPRSS-2 expression in the respiratory tract in mice, independent of disease state. Thus, sex differences in ACE-2 and TMPRSS-2 protein expression observed in mice may not explain the higher disease burden of COVID-19 among men.
【저자키워드】 immunology, Medical research, Diseases, Cardiology, Molecular medicine, 【초록키워드】 COVID-19, Sex, cardiovascular disease, SARS-CoV-2 virus, protease, Sex hormones, angiotensin-converting enzyme 2, kidney, ACE-2, Protein, myocardial injury, mice, female, age, hormone, respiratory tract, correlation, Mouse models, Sex difference, disease, expression, liver, Lung alveoli, association, clinical study, Injury, immunostaining, lung tissue, contrary, protein expression, transmembrane, lower expression, serine 2, men, Alter, Cell, independent, analyzed, addition, indicate, regulated, explain, gonadal, sinusoids, variety of tissue, 【제목키워드】 ACE-2, Protein, murine model, Injury, the SARS-CoV-2,