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

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:duxiaoqingdu
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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. 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 from 6.86 ± 0.51 mm to 6.28 ± 0.37 mm (P <0.05), increased fractioning shortening from 41.4% ± 4.5% to 52.7% ± 4.2% (P <0.01), and the decreased ratio of BNP / GAPDH mRNA levels from 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 the left ventricle tissue were increased increased 18 weeks after sur gery andatorvastatin also prevented those changes. Confound: Left ventricular remod-eling induced by AV fistula was profoundly changed by atorvastatin treatment. Hypertrophy was attenuated and global function was improved. These positive effects of atorvastatin on heart failure were associated with decreased MMP-2 and 9 protein expression and enzyme activity.
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