TY - JOUR
T1 - Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction
AU - Gao, Feng
AU - Kataoka, Masaharu
AU - Liu, Ning
AU - Liang, Tian
AU - Huang, Zhan Peng
AU - Gu, Fei
AU - Ding, Jian
AU - Liu, Jianming
AU - Zhang, Feng
AU - Ma, Qing
AU - Wang, Yingchao
AU - Zhang, Mingming
AU - Hu, Xiaoyun
AU - Kyselovic, Jan
AU - Hu, Xinyang
AU - Pu, William T.
AU - Wang, Jian’an
AU - Chen, Jinghai
AU - Wang, Da Zhi
N1 - Funding Information:
We thank members of the Wang and Chen laboratories for advice and support. We thank Dr. Andrea Ventura (Memorial Sloan Kettering Cancer Center) for providing mouse miR-19a/19b plasmid. This research is supported by National Key R&D Program of China (2017YFA0103700), Grants from National Natural Science Foundation of China (Nos. 81470382, 81670257 for J.C.). Work in the Wang lab is supported by American Heart Association, Muscular Dystrophy Association, and the NIH (HL085635, HL116919, HL138757). M.K. was supported by Banyu Life Science Foundation International. Z.-P.H. was supported by NIH T32HL007572 and American Heart Association Scientist Development Grant (SDG). J.D. was supported by NIH T32HL007572.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-019-09530-1
DO - 10.1038/s41467-019-09530-1
M3 - Article
C2 - 30996254
AN - SCOPUS:85064444048
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1802
ER -