Influence of matrix metalloproteinases on ventricular remodeling following myocardial infarction in the rats

Objective To study the relationship of matrix metallproteinases(MMPs) on ventricular remodeling following myocardial infarction in the rats and the intervening effects of losartan. Methods Eighty-two Sprague-Dawley(SD) rats were randomly divided into the groups of control (group C, n=10), myocardial infarction (group MI, n=36) and losartan group (LT , n=36), the rats of group LT were given losartan 50mg·kg -1 ·d -1 orally and the rats of group LT and group MI were given isoprenaline(ISP)from the second week of the study. 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. The microstructure of myocardium was observed with electron microscope. Results The activities of MMP-2 and MMP-9 in the group MI increased significantly at the 1st, 2nd (P0.01) and 4th week (P0.05) after MI. The collagen amount and I/III collagen ratio increased subsequently. The activity of MMP-2 in the group LT reduced significantly at the 1st, 2nd (P0.01)and 4th week(P0.05) after the onset of study compared with that of group MI. Also did MMP-9's activity at the 1st week (P0.01) and at 2nd and 4th week (P0.05). The collagen amount and I/III collagen ratio decreased accordingly. Conclusion The activity of MMPs in the myocardial interstitium increased following myocardial infarction, then collagen amount raised and I/III collagen ratio increased. These changes may be the major causes of ventricular remodeling. The effects of losartan on the activity of MMPs may be one of mechanisms on the ventricular remodeling following myocardial infarction.