Increased Plasma Concentration of Matrix Metalloproteinase-7 in Patients with Coronary Artery Disease

Abstract

Plaque rupture is often associated with breakdown of the extracellular matrix in the shoulder region of a plaque. We tested whether plasma concentrations of various matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) could serve as markers for plaque instability as well as relationships between plasma MMPs and inflammatory markers. The study group included 65 men with angiographically verified CAD (45 with stable and 20 with unstable CAD) and 28 healthy controls. Circulating MMP, TIMP-1, C-reactive protein, and cytokine concentrations were measured by ELISA. Leukocyte subtype counts in whole blood were determined, and T-cell subsets and natural killer cells were measured by flow cytometry. Differences in continuous variables between groups were tested by ANOVA with the Scheffé F-test used as a post hoc test, and correlations were analyzed by a linear regression method. The plasma concentration of MMP-7 was increased in patients with stable and unstable CAD, whereas MMP-2 and -3 concentrations were decreased. The plasma concentration of TIMP-1 was significantly increased in patients with unstable CAD. MMP-2, -3, and -7 showed no correlations with established markers of inflammation. However, MMP-2 correlated positively with the number of natural killer cells in patients with stable and unstable CAD. Plasma concentrations of MMPs and TIMPs may be markers of CAD but appear to be differentially regulated.