| Objective: Left ventricular remodeling (LVR) includes changes in structure and form, distribution of cardiac myocytes, distribution of extracellular matrix, imbalance of myocardial cells and extracellular matrix, and conformation of the ventricle. LVR plays an important role in the development and deterioration of heart failure (HF). However, the pathogenesis of LVR and HF induced by myocardial infarction (MI) remains unclear, making it difficult to prevent and treat LVR and HF post-MI.In the current study, we investigated changes in interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2) and transforming growth factor beta-1 (TGF-β1) during the process of LVR and HF post-MI. To clarify the relationship between these inflammatory factors and LVR, we also examined the effect of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on IL-6, MMP-2 and TGF-β1.Method: Male Sprague-Dawley rats (SD) were randomly divided into three groups: sham, MI and MI + statin. MI 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 and MI groups were treated with placebo. Rats were sacrificed at day 3, week 4, and week 8. MMP-2 protein (by Western blot) and TGF-β1 expression were determined and collagen volume fraction (CVF) and the ratio of type I to III collagen (by immunohistochemistry) were assessed in the noninfarcted zone. Serum IL-6 levels were examined by ELISA. Left ventricular function was measured physiologically at different times.Results: We found that: 1) MMP-2 and TGF-β1 levels in the noninfarcted zone and serum IL-6 levels were significantly higher in the MI and MI + statin groups than inthe sham group (P < 0.05), but significantly lower in the MI + statin group than in the MI group (P < 0.05) at day 3, week 4, and week 8; 2) CVF and type I /III collagen ratio in the MI + statin group were significantly less than in the MI group (P < 0.05) at week 4 and week 8; and 3) left ventricular function of the MI + statin group was improve compared with the MI group.Conclution: Our results demonstrate that by decreasing MMP-2, IL-6 and TGF-Pi in cardiac muscle in the noninfarcted zone and repressing destruction of the collagen network and deposition of redundant reactive collagen, fluvastatin can both prevent and reverse left ventricular remodeling and improve cardiac function. |
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