Journal
JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 3, Issue 3, Pages 350-362Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2018.01.005
Keywords
hyperinsulinemia; infarct size; microRNA; O-GlcNAcylation
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Funding
- National Institutes of Health, National Heart, Lung, and Blood Institute [RO1HL122815, RO1HL115247, U54 HL117798]
- National Natural Science Foundation of China [81770256]
- Fundamental Research Funds for the Central Universities
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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-GlcNAcytation 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. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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