Aging
Navigate
Submit an Article
Research Paper|Volume 12, Issue 12|pp 11603—11622

Over-expression of microRNA-145 drives alterations in β-adrenergic signaling and attenuates cardiac remodeling in heart failure post myocardial infarction

Zhebo Liu1,2,3, Bo Tao1,2,3, Suzhen Fan1,2,3, Shengyu Cui1,2,3, Yong Pu4, Liqiang Qiu1,2,3, Hao Xia1,2,3, Lin Xu1,2,3
  • 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
  • 2Cardiovascular Research Institute, Wuhan University, Wuhan, PR China
  • 3Hubei Key Laboratory of Cardiology, Wuhan, PR China
  • 4Renmin Hospital of Hannan, Renmin Hospital of Wuhan University, Wuhan, PR China
* Equal contribution
Received: February 18, 2020Accepted: April 28, 2020Published: June 18, 2020
https://doi.org/10.18632/aging.103320

Copyright © 2020 Liu 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: Numerous studies have highlighted the crucial role of microRNA-145 (miR-145) in coronary atherosclerosis and myocardial ischemia reperfusion injury. However, effects of miR-145 on β-adrenergic signaling and cardiac remodeling in heart failure (HF) remains unclarified.

Methods and Results: We established HF model in rats with left anterior descending coronary artery (LAD) occlusion. Four weeks after LAD ligation, rats showed substantial aggravation of cardiac dilation and electrophysiological instability. Up-regulation of miR-145 ameliorated HF-induced myocardial fibrosis and prolonged action potential duration. Echocardiography revealed increased basal contractility and decreased left ventricular inner-diameter in miR-145 over-expressed heart, while cardiac response to β-adrenergic receptor (βAR) stimulation was reduced. Furthermore, miR-145 increased L-type calcium current (ICa) density while decreased ICa response to β-adrenergic stimulation with isoproterenol. The alterations in βAR signaling might be predominant due to miR-145-mediated activation of Akt/CREB cascades. At high frequency pacing, Ca2+ transient, cell shortening and frequency of Ca2+ waves were significantly improved in AD-miR-145 group. Western blotting revealed that increased expression of Cav1.2, Ca2+-ATPase, β2AR, GNAI3 and decreased level of CaMKII might be attributed to the cardioprotective effects of miR-145.

Conclusion: miR-145 effectively alleviates HF-related cardiac remodeling by improving cardiac dilation, fibrosis, intracellular Ca2+ mishandling and electrophysiological instability.