Abstract
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 β1-AR and arrhythmogenesis in acute myocardial infarction (AMI) in rats. β1-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 β1-AR expression at the protein level, without affecting β1-AR mRNA level, in neonatal rat ventricular cells (NRVCs). Silencing of let-7e by let-7e antisense inhibitor (AMO-let-7e) enhanced β1-AR expression at the protein level in NRVCs. Administration of the lentivirus vector containing precursor let-7e (len-pre-let-7e) significantly inhibited β1-AR expression in rats, whereas len-AMO-let-7e up-regulated β1-AR relative to the baseline control level, presumably as a result of depression of tonic inhibition of β1-AR by endogenous let-7e. Len-negative control (len-NC) did not produce significant influence on β1-AR expression. Len-pre-let-7e also profoundly reduced the up-regulation of β1-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 β1-AR blocker. Down-regulation of let-7e contributes to the adverse increase in β1-AR expression in AMI and let-7e supplement may be a new therapeutic approach for preventing adverse β1-AR up-regulation and treating AMI-induced arrhythmia.
Highlights
Acute myocardial infarction (AMI) or heart attack as a result of blockage of a coronary artery in the clinical setting is a common cause of mortality and morbidity worldwide
It occurs after a prolonged period of myocardial ischemia, which can result in cardiac electrophysiological disturbance, haemodynamic disorder, metabolic disorders, necrosis and apoptosis of cardiomyocytes [1, 2], accompanied by abnormal alterations of gene expression such as aberrant regulation of a number of ion channels [3] and badrenoceptors (b-AR) [4, 5], and reduction in connexin43 [6, 7]
Standard lead II digital ECG tracings were recorded for evaluation of arrhythmias using the BL-420F bio-function experiments system (Taimeng, Chengdu, China)
Summary
Acute myocardial infarction (AMI) or heart attack as a result of blockage of a coronary artery in the clinical setting is a common cause of mortality and morbidity worldwide. It occurs after a prolonged period of myocardial ischemia, which can result in cardiac electrophysiological disturbance, haemodynamic disorder, metabolic disorders, necrosis and apoptosis of cardiomyocytes [1, 2], accompanied by abnormal alterations of gene expression such as aberrant regulation of a number of ion channels [3] and badrenoceptors (b-AR) [4, 5], and reduction in connexin43 [6, 7], b-adrenoceptor plays a pivotal role in regulating cardiac function and heart rate (HR). B-AR expression is increased in the acute phase of myocardial infarction [4, 5]; in contrast, it is decreased in chronic heart failure [15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
