miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury

Jing Shi^1*, Yihua Bei^2*, Xiangqing Kong^1✉, Xiaojun Liu³, Zhiyong Lei⁴, Tianzhao Xu², Hui Wang¹, Qinkao Xuan¹, Ping Chen², Jiahong Xu⁵, Lin Che⁵, Hui Liu¹, Jiuchang Zhong⁶, Joost PG Sluijter⁴, Xinli Li¹, Anthony Rosenzweig³, Junjie Xiao^2✉

1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;
2. Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China.
3. Massachusetts General Hospital Cardiovascular Division and Harvard Medical School, Boston, MA 02115, USA.
4. Laboratory of Experimental Cardiology, University Medical Centre Utrecht, Utrecht 3508GA, The Netherlands.
5. Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
6. State Key Laboratory of Medical Genomics & Shanghai Institute of Hypertension, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
^*These authors contributed equally to this work.

Abstract

Limited microRNAs (miRNAs, miRs) have been reported to be necessary for exercise-induced cardiac growth and essential for protection against pathological cardiac remodeling. Here we determined members of the miR-17-92 cluster and their passenger miRNAs expressions in two distinct murine exercise models and found that miR-17-3p was increased in both. miR-17-3p promoted cardiomyocyte hypertrophy, proliferation, and survival. TIMP-3 was identified as a direct target gene of miR-17-3p whereas PTEN was indirectly inhibited by miR-17-3p. Inhibition of miR-17-3p in vivo attenuated exercise-induced cardiac growth including cardiomyocyte hypertrophy and expression of markers of myocyte proliferation. Importantly, mice injected with miR-17-3p agomir were protected from adverse remodeling after cardiac ischemia/reperfusion injury. Collectively, these data suggest that miR-17-3p contributes to exercise-induced cardiac growth and protects against adverse ventricular remodeling. miR-17-3p may represent a novel therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.

Keywords: Exercise, Cardiac growth, microRNA.

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How to cite this article:
Shi J, Bei Y, Kong X, Liu X, Lei Z, Xu T, Wang H, Xuan Q, Chen P, Xu J, Che L, Liu H, Zhong J, Sluijter JP, Li X, Rosenzweig A, Xiao J. miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury. Theranostics 2017; 7(3):664-676. doi:10.7150/thno.15162. Available from http://www.thno.org/v07p0664.htm