2004•Zhongguo linchuang yaolixue yu zhiliaoxueRequires access
Influence of fluvastatin on MMP-2, TGF-β_1 and left ventricular remodeling in rats with heart failure
Dai Ha
Open publisher page 0 citations
Abstract
AIM: To investigate the influence of fluv-astation on matrix metalloproteinase-2 ( MMP-2) and transforming growth factor beta-1 (TCF-β1) in the development of left ventricular remodeling and heart failure of rats after myocardial infarction (MI) and the mechanisms of left ventricular remodeling and heart failure after myocardial infarction. METHODS: 67 male Sprague-Dawley (SD) rats were randomly divided into three groups: the sham group, the MI group and the MI + statin group. The MI model was induced by ligating the left anterior descending coronary artery. After 24 hours of ligation, animals in the MI + statin group were treated with fluvastatin (4 mg·kg-1·d-1 ), and animals in the sham group and the MI group were treated with placebo. Rats were sacrificed 3 days, 4 weeks and 8 weeks after treatment. The content of MMP-2 protein (by Western-blot) and the expression of TGF-β1 were determined, and the collagen volume fraction (CVF) and the ratio of type Ⅰ to Ⅲ collagen (by immunohistochemistry) in the noninfarcted zone were assessed. Left ventricular function was measured atdifferent times. RESULTS: The levels of MMP-2 and TGF-β1 in the noninfarcted zone were significantly higher in the MI group and the MI + statin group than that in the sham group ( P 0.05) , but it was significantly lower in the MI + statin group than that in the MI group ( P 0.05) 3 days, 4 weeks and 8 weeks after treatment. Compared with the MI group, left ventricular function of rats in the MI + statin group was significantly improved. CVF and type Ⅰ /Ⅲ collagen ratio in the MI + statin group were significantly lower than that in the MI group ( P 0.05) 4 weeks and 8 weeks after treatment. CONCLUSION: Fluvastatin can relieve the destruction of the collagen network and deposition of redundant reactive collagen in cardiac muscles through decreasing the MMP-2 and TGF-β1, of cardiac muscle in the noninfarcted zone. Fluvastatin can prevent and reverse the left ventricular remodeling and improve the cardiac function.