Exogenous Bmp-7 Facilitates The Recovery Of Cardiac Function After Acute Myocardial Infarction Through Counteracting Tgf-Beta 1 Signaling Pathway

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE(2018)

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Abstract
Myocardial fibrosis after acute myocardial infarction (AM I) is one of the main causes of myocardial remodeling and heart function abnormalities. Bone morphogenetic protein-7 (BMP-7) has been reported to play essential roles in anti-fibrosis. In this study, we demonstrated the role of exogenous BMP-7 on myocardial fibrosis and heart function recovery after AMI. A rat model of AMI was established via ligation of the left anterior descending coronary artery (LAD). Twenty rats were grouped into sham group which underwent chest open operation, but did not receive LAD ligation. Another 40 rats underwent LAD ligation were randomly grouped into saline-treated group (n = 20) and BMP-7-treated group (n = 20) which received saline treatment or exogenous BMP-7 treatment for 14 days, respectively. Two weeks after LAD ligation, the survival rate of BMP-7-treated AMI group was significantly improved compared to the saline group. Moreover, the cardiac function was preserved as shown by echocardiography examination, and the infarcted size was limited upon BMP-7 treatment. In addition, we investigated the role of TGF-beta 1 signaling pathway in BMP-7-mediated cardioprotective effects by analyzing the expression levels of TGF-beta 1, Smad 2 and Smad 3 in the infarct zone, border zone, and non-infarct zone. Western blot and quantitative PCR results suggested that BMP-7 attenuated myocardial fibrosis through counteracting TGF-beta 1 signaling pathway, thereby exerting cardioprotective effects. In conclusion, our data provide a potential therapeutic direction for preserving cardiac function and improving prognosis of AMI patients.
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Key words
AMI, BMP7, myocardial fibrosis, Smad, TGF-beta 1
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