Role of miR-133a in regulating TGF-β1 signaling pathway in myocardial fibrosis after acute myocardial infarction in rats

B.-T. Yu, N. Yu, Y. Wang, H. Zhang, K. Wan, X. Sun, C.-S. Zhang

Department of Emergency, The Affiliated Central Hospital of Qingdao University, Qingdao, China. zcsys@163.com

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• Cardiology

OBJECTIVE: The aim of this research was to explore the effect of microRNA-133a (miR-133a) on myocardial fibrosis and cardiac function after myocardial infarction in rats, and to investigate the possible regulatory mechanism.

MATERIALS AND METHODS: Myocardial infarction model was successfully established in rats by ligation of the left anterior descending coronary artery. After miR-133a overexpression in rats myocardium, cardiac function was examined by echocardiography. Meanwhile, the degree of myocardial fibrosis was detected by Masson staining. In addition, the expression of α-smooth muscle actin (α-SMA) in cardiomyocytes was detected by immunohistochemistry. Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to analyze the expression level of miR-133a in the junction of myocardial infarction. The mRNA expressions of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen type 1 (col 1), collagen type 3 (col 3) and α-SMA were measured by qRT-PCR as well. Furthermore, the protein levels of the above genes were detected by Western blotting.

RESULTS: MiR-133a expression in the infarct border zone of myocardial tissue was significantly decreased on the 28th day after myocardial infarction surgery (p<0.05). In addition, up-regulation of miRNA-133a in myocardial tissue of rats with myocardial infarction could remarkably improve cardiac function and reduce collagen volume fraction. Furthermore, the mRNA and protein expression levels of TGF-β1, CTGF, col1, col3, α-SMA in myocardial tissue were obviously decreased after miRNA-133a up-regulation (p<0.001).

CONCLUSIONS: Overexpression of miR-133a down-regulates the mRNA and protein levels of TGF-β1 and CTGF after myocardial infarction. Moreover, this may eventually reduce myocardial collagen deposition, inhibit myocardial fibrosis and improve cardiac function.

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