Open Access

ARTICLE

Clinical significance of matrix metalloproteinases activity in acute myocardial infarction

D. P. Papadopoulos¹, I. Moyssakis¹, T. K. Makris¹, M. Poulakou², G. Stavroulakis¹, D. Perrea², V. E. Votteas¹

1 Department of Cardiology, Laiko Hospital of Athens, 6-8 Glykonos street, 106-75 Athens, Greece
2 Department of Experimental surgery and surgical research, Athens Medical School, Greece

* Corresponding Author: D.P. Papadopoulos,

European Cytokine Network 2005, 16(2), 152-160.

Abstract

Matrix metalloproteinases (MMP) degrade myocardial fibrillar collagen in acute myocardial infarction (MI) patients. Their activity is tightly controlled in normal myocardium by a family of closely related tissue inhibitors known as TIMP. An imbalance in their activity might contribute to post-MI remodeling. Plasma levels of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex were measured, using relevant ELISA kits, in 24 (22 males-2 females), acute MI patients with a mean age 59 ± 14 years. Blood samples were taken on admission (0h),and 3h, 6h, 9h, 18h, 24h, 36h, 48h, 3^rd, 4^th, 5^th, 7^th, 15^th, 30^th days after MI. All patients underwent coronary arteriography with ventriculography for estimation of left ventricular ejection fraction (LVEF) and extent of coronary artery diseases, and echocardiographic study for measuring end-diastolic diameter (EDD). Ten patients with an LVEF < 45%, an EDD > 47.5mm, and heart failure symptoms were included in group A and compared against 12 patients with an LVEF > 45% an EDD < 47.5mm in group B.Mean plasma concentrations of MMP-1 were higher by 21% in group A (1.3 ± 0.2 ng/mL) compared to group B (1 ± 0.1 ng/mL) over the total study period. TIMP-1 plasma concentrations showed very little difference between the 2 groups, (704 ± 213 ng/mL versus 691 ± 165 ng/mL, (6%)) Finally, plasma concentrations of MMP-1/TIMP-1 complex were lower by -36% in group A with a mean value of 2.7 ± 0.6 ng/mL versus 3.7 ± 0.5 ng/mL in group B. Mean values for the differences were significant at time points 0, 6, 18, 24 and 48 hours for MMP-1 (p < 0.036), and on 48h and the 4^th day for MMP-1/TIMP-1 complex (p < 0.031). Moreover, a good correlation was found between plasma concentrations of creatine kinase (CK) and MMP-1 at 18h (r = 0.422, p = 0.041) and on the 4^th day (r = 0.67, p = 0.046), and TIMP-1 on the 4^th day (r = 0.67, p = 0.047). Additionally, mean values for LVEF were 35.8 ± 8.8% in group A versus 51.2 ± 1.8% (p = 0.00014) in group B. Also, the EDD in-group A was 52.1 ± 6.9 mm versus 42.9 ± 3.2 mm in group B (p = 0.00013). In acute MI patients, increased MMP-1, with no change in TIMP-1, is associated with left ventricular dysfunction and dilatation, suggesting that increased collagenolytic activity contributes to loss of LV function.

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Keywords

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