Author + information
- Received December 11, 2017
- Revision received January 15, 2018
- Accepted January 16, 2018
- Published online June 25, 2018.
- Dandan Wanga,
- Xiaoyue Hu, MDb,
- Seung Hee Lee, PhDb,
- Feng Chen, BSa,
- Kai Jiang, BSa,
- Zizhuo Tu, BSa,
- Zejian Liu, PhDc,
- Jing Du, MD, PhDb,
- Li Wang, PhDd,
- Chaoying Yin, PhDd,
- Yu Liao, MDe,
- Hongcai Shang, PhDf,
- Kathleen A. Martin, PhDb,
- Raimund I. Herzog, MDc,
- Lawrence H. Young, MDb,
- Li Qian, PhDd,∗ (, )
- John Hwa, MD, PhDb,∗ ( and )
- Yaozu Xiang, MD, PhDa,∗ ()
- aShanghai East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, China
- bSection of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, Connecticut
- cSection of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
- dMcAllister Heart Institute, Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina
- eDepartment of Endocrinology and Metabolism, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- fKey laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- ↵∗Address for correspondence:
Dr. Yaozu Xiang OR Dr. Li Qian OR Dr. John Hwa, Advanced Institute of Translational Medicine, School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 20092, China.
• Optimal treatment for patients with diabetes and myocardial infarction remains a challenge.
• Hyperglycemia- and hyperinsulinemia-induced miR-24 reduction and O-GlcNAcylation in the diabetic heart contributes to poor survival in diabetic myocardial I/R and increased infarct size post-I/R.
• Overexpression of miR-24 in murine hearts significantly reduces myocardial infarct size.
• miR-24 targets multiple key proteins including O-GlcNac transferase, ATG4A (a key protein in autophagy), and BIM (a pro-apoptosis protein) to protect the myocardium from I/R injury.
• miR-24 is a promising therapeutic candidate for diabetic I/R injury.
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.
This work was supported by National Institutes of Health, National Heart, Lung, and Blood Institute grants (RO1HL122815, RO1HL115247, and U54 HL117798 to Dr. Hwa), and grants from the National Natural Science Foundation of China (81770256) and the Fundamental Research Funds for the Central Universities (both to Dr. Xiang). Dr. Young has served as a consultant to Portage Pharmaceuticals; and has received grant support through Yale University from Merck Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received December 11, 2017.
- Revision received January 15, 2018.
- Accepted January 16, 2018.
- 2018 The Authors