Effect of atorvastatin on non-ischemic heart failure and matrix metalloproteinase-2 and 9 in rats.
OBJECTIVE
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/d) 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.


CONCLUSIONS
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.
Cheng
Gang
G
Department of Cardiology, the Second Affiliated Hospital, Zhejiang University, Medical School, Hangzhou 310009, China.
Xu
Geng
G
Cai
Hong-wen
HW
Wang
Hui-hua
HH
Bao
Xiao-feng
XF
D000818:Animals; D001164:Arteriovenous Fistula / Q000473:pathology; D000069059:Atorvastatin; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9