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Diabetes Exacerbates Myocardial Ischemia/Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylation.

ABSTRACT: Management for patients with diabetes experiencing myocardial infarction remains a challenge. Here the authors show that hyperglycemia- and hyperinsulinemia-induced microRNA-24 (miR-24) reduction and O-GlcNAcylation in the diabetic heart contribute to poor survival and increased infarct size in diabetic myocardial ischemia/reperfusion (I/R). In a mouse model of myocardial I/R, pharmacological or genetic overexpression of miR-24 in hearts significantly reduced myocardial infarct size. Experimental validation revealed that miR-24 targets multiple key proteins, including O-GlcNac transferase, ATG4A, and BIM, to coordinately protect the myocardium from I/R injury. These results establish miR-24 as a promising therapeutic candidate for diabetic I/R injury.

SUBMITTER: Wang D 

PROVIDER: S-EPMC6058960 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Diabetes Exacerbates Myocardial Ischemia/Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylation.

Wang Dandan D   Hu Xiaoyue X   Lee Seung Hee SH   Chen Feng F   Jiang Kai K   Tu Zizhuo Z   Liu Zejian Z   Du Jing J   Wang Li L   Yin Chaoying C   Liao Yu Y   Shang Hongcai H   Martin Kathleen A KA   Herzog Raimund I RI   Young Lawrence H LH   Qian Li L   Hwa John J   Xiang Yaozu Y  

JACC. Basic to translational science 20180516 3

Management for patients with diabetes experiencing myocardial infarction remains a challenge. Here the authors show that hyperglycemia- and hyperinsulinemia-induced microRNA-24 (miR-24) reduction and O-GlcNAcylation in the diabetic heart contribute to poor survival and increased infarct size in diabetic myocardial ischemia/reperfusion (I/R). In a mouse model of myocardial I/R, pharmacological or genetic overexpression of miR-24 in hearts significantly reduced myocardial infarct size. Experimenta  ...[more]

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