Let‐7e replacement yields potent anti‐arrhythmic efficacy via targeting beta 1‐adrenergic receptor in rat heart. Issue 7 (24th April 2014)

• Record Type: Journal Article
• Authors: Li, Xin; Wang, Baoqiu; Cui, Hairong; Du, Yue; Song, Yang; Yang, Lei; Zhang, Qi; Sun, Fei; Luo, Dan; Xu, Chaoqian; Chu, Wenfeng; Lu, Yanjie; Yang, Baofeng
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 7(2014)
• Page Start: 1334
• Page End: 1343
• Publication Date: 2014-04-24
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12288
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12288-abs-0001"> <title>Abstract</title> <p>Beta‐adrenoceptor (β‐AR) exerts critical regulation of cardiac function. MicroRNAs (miRNAs) are potentially involved in a variety of biological and pathological processes. This study aimed to investigate the role of miRNA let‐7e in the up‐regulation of β<sub>1</sub>‐AR and arrhythmogenesis in acute myocardial infarction (AMI) in rats. β<sub>1</sub>‐AR expression was significantly up‐regulated and let‐7a, c, d, e and i were markedly down‐regulated in the infarcted heart after 6 and 24 hrs myocardial infarction. Forced expression of let‐7e suppressed β<sub>1</sub>‐AR expression at the protein level, without affecting β<sub>1</sub>‐AR mRNA level, in neonatal rat ventricular cells (NRVCs). Silencing of let‐7e by let‐7e antisense inhibitor (AMO‐let‐7e) enhanced β<sub>1</sub>‐AR expression at the protein level in NRVCs. Administration of the lentivirus vector containing precursor let‐7e (len‐pre‐let‐7e) significantly inhibited β<sub>1</sub>‐AR expression in rats, whereas len‐AMO‐let‐7e up‐regulated β<sub>1</sub>‐AR relative to the baseline control level, presumably as a result of depression of tonic inhibition of β<sub>1</sub>‐AR by endogenous let‐7e. Len‐negative control (len‐NC) did not produce significant influence on β<sub>1</sub>‐AR expression. Len‐pre‐let‐7e also profoundly reduced the up‐regulation of β<sub>1</sub>‐AR induced by AMI and this effect was abolished by len‐AMO‐let‐7e. Importantly, len‐pre‐let‐7e application significantly reduced arrhythmia incidence after AMI in rats and its anti‐arrhythmic effect was cancelled by len‐AMO‐let‐7e. Notably, anti‐arrhythmic efficacy of len‐pre‐let‐7e was similar to propranolol, a non‐selective β‐AR blocker and metoprolol, a selective β<sub>1</sub>‐AR blocker. Down‐regulation of let‐7e contributes to the adverse increase in β<sub>1</sub>‐AR expression in AMI and let‐7e supplement may be a new therapeutic approach for preventing adverse β<sub>1</sub>‐AR up‐regulation and treating AMI‐induced arrhythmia.</p> </abstract>