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

Feng Gao, Masaharu Kataoka, Ning Liu, Tian Liang, Zhan Peng Huang, Fei Gu, Jian Ding, Jianming Liu, Feng Zhang, Qing Ma, Yingchao Wang, Mingming Zhang, Xiaoyun Hu, Jan Kyselovic, Xinyang Hu, William T. Pu, Jian’an Wang, Jinghai Chen, Da Zhi Wang

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20 Citations (Scopus)

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.

Original languageEnglish
Article number1802
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Gao, F., Kataoka, M., Liu, N., Liang, T., Huang, Z. P., Gu, F., Ding, J., Liu, J., Zhang, F., Ma, Q., Wang, Y., Zhang, M., Hu, X., Kyselovic, J., Hu, X., Pu, W. T., Wang, J., Chen, J., & Wang, D. Z. (2019). Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction. Nature communications, 10(1), [1802]. https://doi.org/10.1038/s41467-019-09530-1