Effects of matrix metalloproteinase on ventricular remodeling after myocardial infarction in rats

Objective:To Characterize the time-course of matrix metalloproteinase (MMP-2, 9) and endogenous tissue inhibitor of MMPs(TIMP-1) up-regulation during left ventricular remodeling following myocardial infarction in rats. Method:The descending left coronary artery of male rats (Sprague-Dawley) was ligated to produce a myocardial infarction model. Sixty-eight rats were randomly divided into the groups of control (n=20) and myocardial infarction (n=48). Protein and mRNA extraction was done on left ventricular samples containing scar and myocardium together. Samples were assayed from 1 day to 4 weeks post-MI. The activity of MMPs was measured by zymography and collagen amount by the method of chloramine T, the ratio of Ⅰ/Ⅲ collagen was assessed by immunohistochemical stain. Protein and mRNA of MMP-2, 9, TIMP-1 were determined by Western-Blot and RT-PCR. Result:The collagen amount increased and the ratio of Ⅰ/Ⅲ decreased at the 2nd and 4th week. The activities and amount of MMP-2 in the group I increased significantly at the 1st, 2nd week; MMP-9 at the 1st, 2nd and 4th week. On the contrary, TIMP-1 decreased on the level of protein. On the contrary, TIMP-1 decreased on the level of protein and mRNA. Conclusion:After myocardial infarction, MMP-2, 9 increase significantly on the level of protein and mRNA; TIMP-1 decrease on the level of protein and mRNA; the collagen amount increase and the ratio of Ⅰ/Ⅲ decrease. These changes may be the major causes of ventricular remodeling.