MicroRNA-577 inhibits cardiomyocyte apoptosis induced by myocardial infarction via targeting PARP1

Y.-H. Wang, X.-Y. Zhang, Y.-Q. Han, F. Yan, R. Wu

Department of Cardio-Pulmonary Function, Fuwai Central China Cardiovascular Hospital (Henan Provincial People’s Hospital Heart Centre), Zhengzhou, China. 13513803991@163.com

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• Cardiology

OBJECTIVE: The aim of this study was to investigate whether microRNA-577 could inhibit myocardial infarction (MI)-induced cardiomyocyte apoptosis by regulating poly ADP-ribose polymerase 1 (PARP1).

MATERIALS AND METHODS: MI model was successfully established in mice by ligation of the left anterior descending coronary artery (LAD). The expression levels of microRNA-577 and PARP1 in myocardial tissues of mice were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). MI model in cells was established by hypoxia pre-treatment in primary cardiomyocytes and MCM cells. Subsequently, the expression levels of microRNA-577 and PARP1 in hypoxia preconditioning cardiomyocytes were determined as well. Meanwhile, Caspase3 activity in cardiomyocytes overexpressing microRNA-577 or PARP1 was detected using a relative commercial kit. Furthermore, the binding relationship between microRNA-577 and PARP1 was examined by Dual-Luciferase reporter gene assay.

RESULTS: Infarct size/risk region and risk region/LV in MI group were (62.1±2.2)% and (57.6±1.9)%, respectively. Both of the above two indexes in the MI group were significantly higher than those of the control group. The serum level of LDH in MI mice increased by 2.8-fold when compared with controls. Meanwhile, the expressions of microRNA-577 and PARP1 in myocardial tissues of MI mice were markedly down-regulated in a time-dependent manner. Compared with normoxia preconditioning cardiomyocytes, microRNA-577 expression in hypoxia preconditioning MCM cells and primary cardiomyocytes was remarkably decreased. Dual-Luciferase reporter gene assay confirmed that microRNA-577 could bind to PARP1. After transfection of microRNA-577 mimics, the expression of PARP1 was significantly down-regulated. Moreover, microRNA-577 over-expression inhibited caspase3 expression in hypoxia preconditioning cells, which could be reversed by PARP1 up-regulation. Similarly, microRNA-577 over-expression markedly decreased infarct size, risk region and serum level of LDH in MI mice, which could be reversed by PAPR1 over-expression.

CONCLUSIONS: MicroRNA-577 inhibits MI-induced cardiomyocyte apoptosis by degrading PARP1.

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