Vitamin D Receptor Regulates Oxidative Stress and Apoptosis Via the HIF-1α/HO-1 Pathway in Cardiomyocytes.

Abstract

Acute myocardial infarction (AMI) is a critical cardiovascular disease with high disability and mortality rates, primarily caused by hypoxic injury to myocardial cells. This study investigates the role of the Vitamin D receptor (VDR) in cardiomyocytes under hypoxic conditions. VDR expression was characterized in human and hypoxic cardiomyocytes isolated from mice. To understand the downstream effects of VDR-related pathways, VDR was modulated using shRNA. RXR expression and localization were measured in hypoxic and sh-VDR cardiomyocytes. Oxidative stress and apoptosis levels were assessed and the effect of Vitamin D treatment was evaluated. VDR expression was found to be downregulated in the serum of AMI patients, similar to the hypoxic cardiomyocytes. Knockdown of VDR induced oxidative stress and apoptosis in normoxic cardiomyocytes, which could not be reversed by vitamin D treatment. Knock-down VDR in cardiomyocytes exposed to hypoxic induced apoptosis and reactive oxygen species via the HIF-1α/HO-1 axis. Overexpression VDR alleviated the expression levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. Our results indicated that VDR is crucial in reducing myocardial stress and apoptosis during hypoxic injury.