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Sci Rep. 2021 Dec 14;11(1):23993. doi: 10.1038/s41598-021-03181-3.

Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury.

Scientific reports

Susan Bengs, Alexia Rossi, Martina Haberecker, Nidaa Mikail, Alexander Meisel, Ahmed Haider, Muriel Grämer, Angela Portmann, Atanas Todorov, Christof Schönenberger, Caroline E Gebhard, Gabriela M Kuster, Vera Regitz-Zagrosek, Catherine Gebhard

Affiliations

  1. Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
  2. Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.
  3. Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
  4. Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, Boston, MA, USA.
  5. Intensive Care Unit, University Hospital Basel, Basel, Switzerland.
  6. Department of Cardiology, University Hospital Basel, Basel, Switzerland.
  7. Department of Biomedicine, Myocardial Research, University of Basel, Basel, Switzerland.
  8. Charité, Universitätsmedizin Berlin, Berlin, Germany.
  9. DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
  10. Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland. [email protected].
  11. Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland. [email protected].
  12. Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. [email protected].

PMID: 34907257 DOI: 10.1038/s41598-021-03181-3

Abstract

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.

© 2021. The Author(s).

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