title: Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.
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.
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China.
authors.forename: Jia-Tian
authors.initials: JT
authors.lastname: Cao
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Zhao
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Lin
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Xiao-Cui
authors.initials: XC
authors.lastname: Li
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Tan
authors.affiliation: Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.|The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, 310058, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Li
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, 310058, China.
authors.forename: Cheng-Liang
authors.initials: CL
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, 310058, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, 310058, China.|Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China. huanghefg@hotmail.com.|Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China. huanghefg@hotmail.com.|The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, 310058, China. huanghefg@hotmail.com.
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000473:pathology*; D011897:Random Allocation; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D002120:Calcium Channel Agonists; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D002117:Calcitriol
keywords: Calcitriol; Cardiac remodeling; Polycystic ovary syndrome; Vitamin D