Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury
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 soug...
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Nature Portfolio
2021-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-03181-3 |
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| author | Susan Bengs Alexia Rossi Martina Haberecker Nidaa Mikail Alexander Meisel Achi Haider Muriel Grämer Angela Portmann Atanas Todorov Christof Schönenberger Caroline E. Gebhard Gabriela M. Kuster Vera Regitz-Zagrosek Catherine Gebhard |
| author_facet | Susan Bengs Alexia Rossi Martina Haberecker Nidaa Mikail Alexander Meisel Achi Haider Muriel Grämer Angela Portmann Atanas Todorov Christof Schönenberger Caroline E. Gebhard Gabriela M. Kuster Vera Regitz-Zagrosek Catherine Gebhard |
| author_sort | Susan Bengs |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-88c5b287c46e43ab92785ea3e802b9d1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-88c5b287c46e43ab92785ea3e802b9d12025-01-19T12:25:06ZengNature PortfolioScientific Reports2045-23222021-12-0111111010.1038/s41598-021-03181-3Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injurySusan Bengs0Alexia Rossi1Martina Haberecker2Nidaa Mikail3Alexander Meisel4Achi Haider5Muriel Grämer6Angela Portmann7Atanas Todorov8Christof Schönenberger9Caroline E. Gebhard10Gabriela M. Kuster11Vera Regitz-Zagrosek12Catherine Gebhard13Department of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichInstitute of Pathology and Molecular Pathology, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDivision of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical SchoolDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichDepartment of Nuclear Medicine, University Hospital ZurichIntensive Care Unit, University Hospital BaselIntensive Care Unit, University Hospital BaselDepartment of Cardiology, University Hospital BaselCharité, Universitätsmedizin BerlinDepartment of Nuclear Medicine, University Hospital ZurichAbstract 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.https://doi.org/10.1038/s41598-021-03181-3 |
| spellingShingle | Susan Bengs Alexia Rossi Martina Haberecker Nidaa Mikail Alexander Meisel Achi Haider Muriel Grämer Angela Portmann Atanas Todorov Christof Schönenberger Caroline E. Gebhard Gabriela M. Kuster Vera Regitz-Zagrosek Catherine Gebhard 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 |
| title | Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury |
| title_full | Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury |
| title_fullStr | Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury |
| title_full_unstemmed | Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury |
| title_short | Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury |
| title_sort | immunoreactivity of the sars cov 2 entry proteins ace 2 and tmprss 2 in murine models of hormonal manipulation ageing and cardiac injury |
| url | https://doi.org/10.1038/s41598-021-03181-3 |
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