Aging
Navigate
Submit an Article
Research Paper|Volume 12, Issue 23|pp 23609—23618

Inhibition of Exo-miR-19a-3p derived from cardiomyocytes promotes angiogenesis and improves heart function in mice with myocardial infarction via targeting HIF-1α

Lianping Gou1, Cheng Xue1, Xiaoyan Tang2, Zhiyuan Fang3
  • 1Department of Cardiovascular Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China
  • 2Department of General Practitioner, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China
  • 3Department of Medicine, Shanxi Provincial People’s Hospital, Xi’an, Shanxi Province, China
Received: April 2, 2020Accepted: June 5, 2020Published: December 11, 2020
https://doi.org/10.18632/aging.103563

Copyright: © 2020 Gou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Myocardial infarction (MI), a common presentation for cardiovascular disease, is caused by reduction of blood flow and oxygen supply and is one of the main causes of death worldwide. MicroRNAs participate in multiple physiological and pathological processed and play crucial role in myocardial infarction.

Results: qRT-PCR analysis showed that expression level of miR-19a-3p was increased in serum of patient with MI. In vitro study indicated that the miR-19a-3p level was upregulated in response to H2O2 treatment and transferred by exosome, and then, uptake occurred in endothelial cells. Furthermore, western blot and immunostaining showed that treatment of exosome enriched miR-19a-3p suppressed the proliferation of endothelial cells and induced cell death, which was inhibited by AMO-19 transfection. Administration of antagomiR-19a-3p promoted angiogenesis and improved heart function of MI mice. Moreover, miR-19a-3p overexpression downregulated the protein level of HIF-1α and transfection of si-HIF-1α reversed the promotion of endothelial cells proliferation caused by AMO-19 transfection. In addition, antagomiR-19a-3p treatment accelerated angiogenesis and infection of AAV5-shHIF-1α inhibited that effect in MI mice.

Conclusions: In conclusion, our finding indicated that miR-19a-3p inhibited endothelial cells proliferation and angiogenesis via targeting HIF-1α and attenuated heart function of mice after MI, and suggested a new mechanism of cell-to-cell communication between cardiomyocytes and endothelial cells.