Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction
Simin Yang,
Chunmiao Wang,
Chengshao Ruan,
Meiling Chen,
Ran Cao,
Liang Sheng,
Naiying Chang,
Tong Xu,
Peiwen Zhao,
Xuesheng Liu,
Fengqin Zhu,
Qingzhong Xiao,
Shan Gao
Affiliations
Simin Yang
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Chunmiao Wang
Department of Cardiology, The First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
Chengshao Ruan
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Meiling Chen
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Ran Cao
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Liang Sheng
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Naiying Chang
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Tong Xu
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Peiwen Zhao
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Xuesheng Liu
Department of Anesthesiology, The First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
Fengqin Zhu
Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China
Qingzhong Xiao
Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
Shan Gao
Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China
Background: Increasing evidence indicates that vitamin D deficiency negatively affects the cardiovascular system. Here we studied the therapeutic effects of calcitriol in myocardial infarction (MI) and investigated its underlying mechanisms. Methods: A MI model of Kun-ming mice induced by left anterior descending coronary artery ligation was utilized to study the potential therapeutic effects of calcitriol on MI. AC16 human cardiomyocyte-like cells treated with TNF-α were used for exploring the mechanisms that underlie the cardioprotective effects of calcitriol. Results: We observed that calcitriol reversed adverse cardiovascular function and cardiac remodeling in post-MI mice. Mechanistically, calcitriol suppressed MI-induced cardiac inflammation, ameliorated cardiomyocyte death, and promoted cardiomyocyte proliferation. Specifically, calcitriol exerted these cellular effects by upregulating Vitamin D receptor (VDR). Increased VDR directly interacted with p65 and retained p65 in cytoplasm, thereby dampening NF-κB signaling and suppressing inflammation. Moreover, up-regulated VDR was translocated into nuclei where it directly bound to IL-10 gene promoters to activate IL-10 gene transcription, further inhibiting inflammation. Conclusion: We provide new insights into the cellular and molecular mechanisms underlying the cardioprotective effects of calcitriol, and we present comprehensive evidence to support the preventive and therapeutic effects of calcitriol on MI.
