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Nat Commun. 2019 Apr 17;10(1):1802. doi: 10.1038/s41467-019-09530-1.

Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction.

Author information

1
Department of Cardiology, The Second Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, 310029, Hangzhou, China.
2
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.
3
Department of Cardiology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
4
Center for Translational Medicine, The First Affiliated Hospital, NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, 510080, China.
5
Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.
6
Faculty of Pharmacy, Comenius University, Bratislava, 832 32, Slovak Republic.
7
Harvard Stem Cell Institute, Harvard University, Cambridge, MA, 02138, USA.
8
Department of Cardiology, The Second Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, 310029, Hangzhou, China. jinghaichen@zju.edu.cn.
9
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA. Da-Zhi.Wang@childrens.harvard.edu.
10
Harvard Stem Cell Institute, Harvard University, Cambridge, MA, 02138, USA. Da-Zhi.Wang@childrens.harvard.edu.

Abstract

The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure.

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