The combination treatment of angiotensin II receptor antagonist and aldosterone receptor antagonist modulates matrix metalloproteinase-2 expression and activity in infarcted myocardium

Matrix metalloproteinase-2(MMP-2) is closely associated with ventricular remodeling after myocardial infarction(MI). Angiotensin II receptor antagonist and aldosterone receptor antagonist prevent ventricular remodeling after MI. However, the effect of the combination of these two antagonists on MMP-2 expression and activity has not been precisely established. Hence, we investigated how the combination influences MMP-2 expression. We used Western blot and immunohistochemistry for observing MMP-2 and the tissue inhibitor of metalloproteinase-2 expression, and zymography for detecting MMP-2 activity. In the no treatment group, MMP-2 expression and activity decreased according to the time course from 1 week to 3 weeks. In irbesartan group, the trend of the increase in MMP-2 expression and activity was observed and compared with the no treatment group at 3 weeks however, there were no statistical differences. In the combination group, there was a statistically significant increase in the MMP- 2 expression and activity, when compared with the no treatment and irbesartan group at 3 weeks. However, these phenomena were not observed at 1 week. Thus, it can be concluded that the combination treatment does not simply inhibit or promote the MMP-2 expression and activity, but modulate it more strongly than irbesartan monotherapy.