Effect of atorvastatin on non-ischemic heart failure and matrix metalloproteinase-2 and 9 in rats

<正> Aim:To examine the role of atorvastatin on volume-overload-induced heart fail-ure and to test the hypothesis that atorvastatin inhibits MMP-2 and 9 expressionin heart failure with non-ischemic etiology.Methods:Arteriovenous （AV） fistula-treated rats were administered with atorvastatin (3 mg·kg-1·d-1) or vehicle for 17weeks.Ventricular hypertrophy and heart failure were assessed by echocardio-graphy,B-type natriuretic peptide BNP mRNA level and morphological measure-ment.MMP-2,9 expression were measured by Western blot and zymography.Results:Atorvastatin decreased left ventricular end diastolic diameter from6.86±0.51 mm to 6.28±0.37 mm （P<0.05）,increased fractioning shortening from41.4%±4.5% to 52.7%±4.2% （P<0.01）,decreased ratio of BNP/GAPDH mRNA levelfrom 0.43±0.03 to 0.27±0.03 （P<0.05）.Similar data were observed for morphologi-cal measurement.Protein expression and enzyme activity of MMP-2 and 9 in theleft ventricle tissue were significantly increased 18 weeks after surgery andatorvastatin also prevented those changes.Conclusion:Left ventricular remod-eling induced by AV fistula was profoundly changed by atorvastatin treatment.Hypertrophy was attenuated and global function was improved.These positiveeffects of atorvastatin on heart failure were associated with decreased MMP-2and 9 protein expression and enzyme activity.