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Vitamin D Receptor Activation Protects against Myocardial Reperfusion Injury through Inhibition of Apoptosis and Modulation of Autophagy.
MedLine Citation:
PMID:  25365634     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims: To determine the roles of vitamin D receptor (VDR) in ischemia/reperfusion-induced myocardial injury and to investigate the underlying mechanisms involved. Results: The endogenous VDR expression was detected in the mouse heart, and myocardial ischemia/reperfusion (MI/R) upregulated VDR expression. Activation of VDR by natural and synthetic agonists reduced myocardial infarct size and improved cardiac function. Mechanistically, VDR activation inhibited endoplasmic reticulum (ER) stress (determined by the reduction of CCAAT/enhancer-binding protein homologous protein expression and caspase-12 activation), attenuated mitochondrial impairment (determined by the decrease of mitochondrial cytochrome c release and caspase-9 activation), and reduced cardiomyocyte apoptosis. Furthermore, VDR activation significantly inhibited MI/R-induced autophagy dysfunction (determined by the inhibition of Beclin 1 over-activation, the reduction of autophagosomes, the LC3-II/LC3-I ratio, and p62 protein abundance, and the restoration of autophagy flux). Moreover, VDR activation inhibited MI/R-induced oxidative stress through a metallothionein-dependent mechanism. The aforementioned cardioprotective effects of VDR agonists were impaired in the setting of cardiac-specific VDR silencing. In contrast, adenovirus-mediated cardiac VDR overexpression decreased myocardial infarct size and improved cardiac function through attenuating oxidative stress, and inhibiting apoptosis and autophagy dysfunction. Innovation and Conclusion: Our data demonstrate that VDR is a novel endogenous self-defensive and cardioprotective receptor against MI/R injury, via mechanisms (at least in part) reducing oxidative stress, and inhibiting apoptosis and autophagy dysfunction-mediated cell death.
Authors:
Tianbao Yao; Xiaoying Ying; Yichao Zhao; Ancai Yuan; Qing He; Huan Tong; Song Ding; Junling Liu; Xu Peng; Erhe Gao; Jun Pu; Ben He
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-3
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-3     Completed Date:  -     Revised Date:  2014-11-5    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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