Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction.

Abstract

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.

• Authors: 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
• Journal: Cells (Cells) Vol. 11 Issue 10 (05 18 2022) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 35626713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-10
• Calcitriol

Topics

• Animals
• Calcitriol (pharmacology, therapeutic use)
• Disease Models, Animal
• Inflammation (metabolism)
• Interleukin-10 (metabolism)
• Mice
• Myocardial Infarction (metabolism)
• Myocytes, Cardiac (metabolism)
• Ventricular Remodeling (physiology)