MicroRNA-29b upregulation improves myocardial fibrosis and cardiac function in myocardial infarction rats through targeting SH2B3

Y. Wang, B.-J. Jin, Q. Chen, B.-J. Yan, Z.-L. Liu

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. lzl6585@sina.com

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• Cardiology

OBJECTIVE: Myocardial fibrosis (MF) seriously affects normal cardiac function. Meanwhile, MF at post-myocardial infarction (MI) is the leading cause of cardiac dysfunction in patients with acute myocardial infarction (AMI). Therefore, the aim of this study was to investigate the potential effect of microRNA-29b on MF and cardiac function after MI in rats.

MATERIALS AND METHODS: In vivo MI model was constructed by ligation of the left anterior descending coronary artery in Sprague-Dawley rats. Lentivirus overexpressing microRNA-29b was established and transfected to up-regulate microRNA-29b expression in rat myocardial tissues. The effect of microRNA-29b on luciferase activity of SH2B3 3’UTR was detected by the luciferase reporter gene assay. The mRNA levels of microRNA-29b, SH1B3, COL1A1, and α-SMA in the infarct border zone and cardiomyocytes were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, the protein levels of SH1B3, COL1A1, and α-SMA in the MI border zone and cardiomyocytes were determined by Western blot. In addition, cardiac function and MF in MI rats were evaluated by echocardiography, hematoxylin and eosin (HE) and Masson staining, respectively.

RESULTS: MicroRNA-29b expression decreased significantly in the infarct border zone at day 28 after MI (p<0.05). In addition, microRNA-29b overexpression in myocardial tissues of MI rats significantly improved impaired cardiac function, reduced collagen volume fraction and down-regulated the expressions of COL1A1 and ɑ-SMA. Subsequent luciferase reporter gene assay verified the binding relation between microRNA-29b and SH2B3. Furthermore, the expressions of COL1A1 and ɑ-SMA were confirmed negatively regulated by SH2B3.

CONCLUSIONS: MicroRNA-29b overexpression alleviates MF and cardiac dysfunction in MI rats through targeting SH2B3.

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