Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19
The susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9746 |
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| author | Samar Rezq Alexandra M. Huffman Jelina Basnet Licy L. Yanes Cardozo Damian G. Romero |
| author_facet | Samar Rezq Alexandra M. Huffman Jelina Basnet Licy L. Yanes Cardozo Damian G. Romero |
| author_sort | Samar Rezq |
| collection | DOAJ |
| description | The susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with obesity, hyperandrogenism, and cardiometabolic dysregulations. We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal androgen exposure model of PCOS. Peripubertal female mice were treated with dihydrotestosterone (DHT) and low (LFD) or high (HFD) fat diet for 90 days. HFD exacerbated DHT-induced increase in body weight, fat mass, and cardiac and renal hypertrophy. In the heart, DHT upregulated AR protein in both LFD and HFD, ACE2 in HFD, and ADAM17 in LFD. In the kidney, AR protein expression was upregulated by both DHT and HFD. Moreover, ACE2 and ADAM17 were upregulated by DHT in both diets. Renal TMPRSS2, furin, and cathepsin L were upregulated by DHT and differentially modulated by the diet. DHT upregulated urinary ACE2 in both diets, while neither treatment modified serum ACE2. Renal AR mRNA expression positively correlated with Ace2, Tmprss2, furin, cathepsin L, and ADAM17. Our findings suggest that women with PCOS could be a population with a high risk of COVID-19-associated cardiac and renal complications. Furthermore, our study suggests that weight loss by lifestyle modifications (i.e., diet) could potentially mitigate COVID-19-associated deleterious cardiorenal outcomes in women with PCOS. |
| first_indexed | 2024-03-10T07:36:38Z |
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| language | English |
| last_indexed | 2024-03-10T07:36:38Z |
| publishDate | 2021-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4f2f9b158d634173a09f3b9d99c151402023-11-22T13:26:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218974610.3390/ijms22189746Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19Samar Rezq0Alexandra M. Huffman1Jelina Basnet2Licy L. Yanes Cardozo3Damian G. Romero4Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USADepartment of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USAThe susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with obesity, hyperandrogenism, and cardiometabolic dysregulations. We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal androgen exposure model of PCOS. Peripubertal female mice were treated with dihydrotestosterone (DHT) and low (LFD) or high (HFD) fat diet for 90 days. HFD exacerbated DHT-induced increase in body weight, fat mass, and cardiac and renal hypertrophy. In the heart, DHT upregulated AR protein in both LFD and HFD, ACE2 in HFD, and ADAM17 in LFD. In the kidney, AR protein expression was upregulated by both DHT and HFD. Moreover, ACE2 and ADAM17 were upregulated by DHT in both diets. Renal TMPRSS2, furin, and cathepsin L were upregulated by DHT and differentially modulated by the diet. DHT upregulated urinary ACE2 in both diets, while neither treatment modified serum ACE2. Renal AR mRNA expression positively correlated with Ace2, Tmprss2, furin, cathepsin L, and ADAM17. Our findings suggest that women with PCOS could be a population with a high risk of COVID-19-associated cardiac and renal complications. Furthermore, our study suggests that weight loss by lifestyle modifications (i.e., diet) could potentially mitigate COVID-19-associated deleterious cardiorenal outcomes in women with PCOS.https://www.mdpi.com/1422-0067/22/18/9746polycystic ovary syndromeCOVID-19SARS-CoV-2angiotensin converting enzyme 2androgensobesity |
| spellingShingle | Samar Rezq Alexandra M. Huffman Jelina Basnet Licy L. Yanes Cardozo Damian G. Romero Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19 International Journal of Molecular Sciences polycystic ovary syndrome COVID-19 SARS-CoV-2 angiotensin converting enzyme 2 androgens obesity |
| title | Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19 |
| title_full | Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19 |
| title_fullStr | Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19 |
| title_full_unstemmed | Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19 |
| title_short | Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19 |
| title_sort | cardiac and renal sars cov 2 viral entry protein regulation by androgens and diet implications for polycystic ovary syndrome and covid 19 |
| topic | polycystic ovary syndrome COVID-19 SARS-CoV-2 angiotensin converting enzyme 2 androgens obesity |
| url | https://www.mdpi.com/1422-0067/22/18/9746 |
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