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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2004, Vol. 9 ›› Issue (11): 1243-1247.

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Influence of fluvastatin on MMP-2, TGF-β1 and left ventricular remodeling in rats with heart failure

MA Jing, WANG Hong, HA Dai-Wen, XU Jiang1   

  1. Department of Internal Medicine and Geriatrics, Zhongnan Hospital, Wuhan University; Institute of Geriatrics; 1Department of Physiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei, China
  • Received:2004-08-24 Revised:2004-09-24 Online:2004-11-26 Published:2020-11-19

Abstract: AIM: To investigate the influence of fluv-astation on matrix metalloproteinase-2 (MMP-2) and transforming growth factor beta-1 (TGF-β1) in the devel-opment of left ventricular remodeling and. heart failure of rats after myocardial infarction (MI) and the mechaiiisms of left ventricular remodeling and heart failure after myo-cardial infarction. METHODS: 67 male Spragiie-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 de-scending coronary artery. After 24 hours of ligation, ani-mals 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 sacri-ficed 3 days, 4 weeks and 8 weeks after treatment. The content of MMP-2 protein (by Western-blot) and the ex-pression of TGF-β1 were detemiined, and the collagen vol-ume fraction (CVF) and the ratio of type I to HI colla-gen (by immunohistochemistry) in the noninfarcted zone were assessed. Left ventricular function was measured at different times. RESULTS: Tlie levels of MMP-2 and TGF-pj 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/IE 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 destmction of the col-lagen network and deposition of redundant reactive colla-gen in cardiac muscles through decreasing the MMP-2 and TGF-β1 of cardiac muscle in the noninfarcted zone. Fluv-astatin can prevent and reverse the left ventricular remod-eling and improve the cardiac function.

Key words: fluvastatin, heart failure, ventriculai remodeling, MMP-2, TGF-β1

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