Effect of angiotensin-converting enzyme inhibitor on collagenolytic enzyme activity in patients with acute myocardial infarction.

Abstract

Matrix metalloproteinases and their tissue inhibitors are key enzymes degrading myocardial collagen in acute myocardial infarction (AMI). The aim of the present study was to determine whether angiotensin-converting enzyme inhibitors (ACEI) influence collagenase-1 (MMP-1) and their tissue inhibitor (TIMP-1) activity in AMI patients. Plasma levels of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex were measured in 24 patients (aged 58.4 +/- 13.9 years) with AMI. Thirteen patients received perindopril 4 mg/day (group A) and 11 did not (group B). Plasma samples collected on admission and at 0, 3, 6, 9, 12, 18, 24, 36 and 48 hours and on days 3, 4, 5, 7, 15 and 30 thereafter were analyzed by relevant ELISA kits. Ejection fraction (EF) was assessed by ventriculography and end-diastolic diameter (EDD) echo-study on days 6 and 30. Values of collagenolytic enzymes of group A compared with those in group B were on average lower by 34%, 18.3% and 40%, respectively. The difference in values between groups at 0 h, 3 h and 9 h was significant (p < 0.048). ANOVA repeated measurement analysis showed significance within subjects for MMP-1 alone (p < 0.043) and for MMP-1 and ACEI (p < 0.046), while for TIMP-1 and MMP-1/TIMP-1 complex significance was only p < 0.0009. Regarding EDD changes, patients in group A showed minimal or no changes (51.23 +/- 1.8 mm to 51.6 +/- 2.13 mm), their EF was 38.8% and infarct size was medium to large. In contrast, group B showed a trend to increase EDD (41 +/- 0.78 mm to 42.33 +/- 0.59 mm), their EF was 50.5% and infarct size was small to medium. In conclusion, early initiation of ACEI treatment reduces collagenolytic activity. This effect may be considered an alternative mechanism for beneficial effects on postinfarction remodeling.