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Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome

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Abstract

Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

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Acknowledgments

This work was supported by Grants from the National Basic Research Program of China (No. 2012CB944900), the National Science and Technology Support Program (No. 2012BAI32B01), Natural Science Foundation of China (Nos. 31171444, 30973209 and 81270708), and Major Scientific and Technological Special Focus on Social Development Project of the Science and Technology Department of Zhejiang province (No. 2010C13028).

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Authors and Affiliations

  1. The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China

    Ling Gao, Yan Liang, Xian-Hua Lin, Xiao-Cui Li, Ya-Jing Tan & He-Feng Huang

  2. Department of Cardiology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China

    Jia-Tian Cao

  3. Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Yi-Chao Zhao

  4. Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China

    Jing-Yi Li & He-Feng Huang

  5. The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, 310058, China

    Jing-Yi Li, Cheng-Liang Zhou, Hai-Yan Xu, Jian-Zhong Sheng & He-Feng Huang

  6. Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, 310058, China

    Jian-Zhong Sheng

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  1. Ling Gao
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Gao, L., Cao, JT., Liang, Y. et al. Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome. Endocrine 52, 363–373 (2016). https://doi.org/10.1007/s12020-015-0797-1

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