Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19

Samar Rezq; Alexandra M. Huffman; Jelina Basnet; Licy L. Yanes Cardozo; Damian G. Romero

doi:10.3390/ijms22189746

journal article Open Access Sep 09, 2021

Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19

Samar Rezq

Alexandra M. Huffman Jelina Basnet Licy L. Yanes Cardozo

Damian G. Romero

International Journal of Molecular Sciences Vol. 22 No. 18 pp. 9746 · MDPI AG

View at Publisher Save 10.3390/ijms22189746

Abstract

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.

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Details

Published: Sep 09, 2021
Vol/Issue: 22(18)
Pages: 9746
License: View

Authors

S

Samar Rezq

Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Women’s Health Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Cardio Renal Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt

A

Alexandra M. Huffman

Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Women’s Health Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Cardio Renal Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA

J

Jelina Basnet

Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Women’s Health Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Cardio Renal Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA

L

Licy L. Yanes Cardozo

Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Women’s Health Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Cardio Renal Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Department of Medicine, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA

D

Damian G. Romero

Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Women’s Health Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA; Cardio Renal Research Center, University of Mississippi Medical Center, 2500 N, State Street, Jackson, MS 39216, USA

Funding

National Institute of General Medical Sciences Award: P20GM121334

National Heart, Lung, and Blood Institute Award: P01HL51971

National Institute of Diabetes and Digestive and Kidney Diseases Award: R21DK113500

Cite This Article

Samar Rezq, Alexandra M. Huffman, Jelina Basnet, et al. (2021). 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, 22(18), 9746. https://doi.org/10.3390/ijms22189746

Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19

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