Abstract
Aim:
To examine the role of atorvastatin on volume-overload-induced heart failure and to test the hypothesis that atorvastatin inhibits MMP-2 and 9 expression in 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 17 weeks. Ventricular hypertrophy and heart failure were assessed by echocardiography, B-type natriuretic peptide BNP mRNA level and morphological measurement. 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), decreased ratio of BNP/GAPDH mRNA level from 0.43±0.03 to 0.27±0.03 (P<0.05). Similar data were observed for morphological measurement. Protein expression and enzyme activity of MMP-2 and 9 in the left ventricle tissue were significantly increased 18 weeks after surgery and atorvastatin also prevented those changes.
Conclusion:
Left ventricular remodeling 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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Project supported by a grant from Research Funding for Distinguished Young Scholars in Medicine of Zhejiang Province, China (No 2004QN011).
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Cheng, G., Xu, G., Cai, Hw. et al. Effect of atorvastatin on non-ischemic heart failure and matrix metalloproteinase-2 and 9 in rats. Acta Pharmacol Sin 28, 511–517 (2007). https://doi.org/10.1111/j.1745-7254.2007.00515.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00515.x
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