Diabetes Exacerbates Myocardial Ischemia/Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylation.
| Citation | Wang, Dandan, et al. “Diabetes Exacerbates Myocardial Ischemia Reperfusion Injury by Down-Regulation of MicroRNA and Up-Regulation of O-GlcNAcylation”. 2018. JACC. Basic to Translational Science, vol. 3, no. 3, 2018, pp. 350–362. |
| Center | Yale University |
| Author | 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, Yaozu Xiang |
| Keywords | ATG4A, autophagy-related gene 4a, BIM, Bcl-2-like protein 11, CVD, cardiovascular disease, DM, diabetes mellitus, I/R, ischemia/reperfusion, MI, myocardial infarction, O-GlcNAcylation, OGT, O-GlcNac transferase, Hyperinsulinemia, infarct size, microRNA |
| 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. |
| Year of Publication |
2018
|
| Journal |
JACC. Basic to translational science
|
| Volume |
3
|
| Issue |
3
|
| Number of Pages |
350-362
|
| Date Published |
06/2018
|
| ISSN Number |
2452-302X
|
| DOI |
10.1016/j.jacbts.2018.01.005
|
| Alternate Journal |
JACC Basic Transl Sci
|
| PMID |
30062222
|
| PMCID |
PMC6058960
|
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