A Carvedilol-responsive MicroRNA, MiR-125b-5p Protects the Heart from Acute Myocardial Infarction by Repressing Pro-apoptotic Bak1 and Klf13 in Cardiomyocytes

Overview

Journal J Mol Cell Cardiol

Specialty Cardiology & Vascular Diseases

Date 2017 Nov 11

PMID 29122578

Citations 50

Authors

Ahmed S Bayoumi

Kyoung-Mi Park

Yongchao Wang

Jian-Peng Teoh

Tatsuya Aonuma

Yaoliang Tang

Huabo Su

Neal L Weintraub

Il-Man Kim

Affiliations

Soon will be listed here.

Abstract

Background: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart. We hypothesize that β-adrenergic receptor/β-arrestin1-responsive miR-125b-5p confers the improvement of cardiac function and structure after acute myocardial infarction.

Methods And Results: Using cultured cardiomyocyte (CM) and in vivo approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit increased susceptibility to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, the improvement of cardiac function and structure elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes Bak1 and Klf13 in CMs.

Conclusions: In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.

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