Effect of Atorvastatin on Serum MMP-2, MMP-9 and TIMP-1 in Rabbits with Chronic Heart Failure

Abstract

Objective To observe the effects of atorvastatin on serum matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), and the tissue inhibitor of metalloproteinase-1(TIMP-1) in the development of chronic heart failure. To investigate the role of atorvastatin in the therapy of chronic heart failure and determine its possible mechanism of action. Methods Thirty Japanese Big Ear rabbits were randomly selected and divided into 3 groups: sham-operated group(SO group), heart failure control group(HC group) and heart failure atorvastatin therapy group(HA group), with 6, 12 and 12 animals in the respective groups. Volume overloading was produced in the HC group and HA group animals by creating an aortic insufficiency, induced by damaging the aortic valve with a catheter introduced through the carotid artery. After 14 days, abdominal aorta constriction was performed in order to obtain a pressure overload. Six weeks later rabbits in the HA group were administered atorvastatin 3mg. Kg −1.d −1 for 4 weeks, at which time the experiment was terminated. Arterial blood was drawn and serum levels of MMP-2, MMP-9 and TIMP-1 were measured in all groups at the same time using an ELISA method. Results Structural and functional indicators of chronic heart failure(CHF) were seen in both the HC and HA groups, but atorvastatin significantly reduced the observed effects. The serum concentrations of MMP-2, MMP-9 and TIMP-1 were at low levels in all three groups at the start of the study, with no difference between them( P < 0.05). At the end of 6th week concentrations were significantly increased in the HC and HA groups compared with the SO group( P < 0.05), but there were no differences between the HC group and HA group( P > 0.05). The increased concentrations in HC group continued to the end of the experiment, but values in the HA group were all lower than those in the HC group by the end of the experiment( P < 0.05). Conclusion Serum concentrations of MMP-2, MMP-9 and TIMP-1 increase significantly during the course of CHF, paralleling the pathological progress of CHF. Atorvastatin benefits CHF, and the decreased serum levels of MMP-2, MMP-9 and TIMP-1 may be one of the drug's mechanism of action.