Diabetes Exacerbates Myocardial Ischemia Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylation
Dandan Wang, Xiaoyue Hu, Seung Hee Lee, Feng Chen, Kai Jiang, Zizhuo Tu, Zejian Liu, Jing Du, Li Wang, Chaoying Yin, Yu Liao, Hongcai Shang, Kathleen A. Martin, Raimund I. Herzog, Lawrence H. Young, Li Qian, John Hwa and Yaozu Xiang
We observed an increase in mortality post-myocardial infarction or ischemia reperfusion (I/R) in type 2 diabetic mice. We also found a reduction of plasma and heart miR-24 levels in diabetic mice. Systemic enrichment of miR-24 in db/db mice or cardiomyocyte-specific overexpression of miR-24 in wild-type (WT) mice significantly reduced myocardial infarct size and alleviated cardiac injury. The possible mechanism underlying miR-24–based therapeutics in diabetic ischemia reperfusion may involve O-GlcNac transferase (OGT)–mediated heart protein O-GlcNAcylation, autophagy-related gene 4a (ATG4A)–mediated autophagy, and Bcl-2-like protein 11 (BIM)–mediated apoptosis.