The Relationship Between Matrix Metalloproteinases-9, Transforming Growth Factor-betal And The Human Atherosclerotic Plaque Stability

Objective: To further study the formative mechanism, effect factors of human unstable atherosclerotic plaque and to discovery the potential clinical unstable plaque marker and the therapeutic strategy of stabilizing plaque. Methods:1) 41 specimen of human coronary artery atherosclerotic plaque were obtained from patients undergoing cardiovascular surgery, and then were routine paraffin embedded, sectioned at 4 m, and stained with hematoxylin and eosin. They were divided into stable (with no or only little lipid core) and unstable plaques(with lipid core size >40%) according to the structure under the opticalmicroscope, performing the qualitive and quantitive analyses of MMP-9, TGF-pl and TR-1 by using immunohistochemical staining technique and auto picture analysis system.2) The duplex ultrasonography was performed in the carotid arteries of all the 120 patients with cerebral infarction located in internal carotid arterial system. 84 patients were included and were divided into soft plaque group, hard plaque group and nonplaque group. Serum MMP-9 levels were determined by enzyme-linked immunosorbent assay in blood samples obtained 3 weeks later after hospitalization.Results:1) The immunopositive stain of MMP-9, TGF- 1 and T R-1 were all located in the vascular smooth muscle cells, endothelial cells, fibroblast, and particularly in the foam cells and macrophage in the atherosclerotic plaque tissue. The protein expression of MMP-9 in the unstable plaques was much stronger than that in the stable ones, and was also stronger on the shoulder of the plaque, in the foam cells and macrophage around the lipid core, while the protein expression of TGF-pl was much stronger in the stable plaques. There were no significant difference for immunopositive stain of TpR- I between the stable and unstable plaques. Con-elation analysis showed that there was a negative correlation between the expression of MMP-9 and TGF-pl with both average area density and averageoptical density (r=-0.332, P=0.034 for average area density; r=-0.373, P=0.016 for average optical density) .2) Carotid plaques were found in 87 (72.5%) patients, the prevalence of severe lumen stenosis was 4.17%. The incidence of soft plaque in same side of cerebral infarction were higher than that of noninfarction. Serum MMP-9 level was significantly higher in soft plaque group than that in the hard plaque and non-plaque group (481.76 161.5 vs 318.67 96.68 vs 237.85 65.34, P<0.05) . Conclusions : There was a close relationship between MMP-9, TGF-pl and plaque stability. Enhanced production MMP-9 may participate in the formation of unstable plaque, while TGF-pl maybe an important stabilizing factor to prevent the transition into an unstable plaque phenotype. MMP-9 may be a potential clinical serum marker of unstable plaque.