Gelatinases [Matrix Metalloproteinase-2 (MMP-2) and MMP-9] Induce Carotid Plaque Instability But Their Systemic Levels Are Not Predictive of Local Events

Matrix metalloproteinases (MMPs) appear to play a central role in atherosclerotic plaque remodeling; however, the relationship of increased MMP levels in inducing carotid plaque instability remains controversial. We investigated whether gelatinases (MMP-2 and MMP-9) are implicated in carotid intraplaque hemorrhage and whether their serum levels may predict local carotid events. Nineteen carotid specimens obtained by endarterectomy of 18 patients were studied. The presence of gross intraplaque hemorrhage was recorded before plaque removal and quantification of MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) in extracts from (1) the more stenotic area of the plaque, (2) the periphery of the plaque, and (3) serum was performed by enzyme-linked immunosorbent assay. MMP-9 levels measured in extracts from the most stenotic area were significantly higher in patients with intraplaque hemorrhage (p = 0.007); however, serum levels showed no difference, while those taken from the periphery of the lesion were also increased but did not reach a statistically significant level (p = 0.06). An increase in MMP-2 values was observed in the periphery of the lesion (p = 0.04) in patients with intraplaque hemorrhage. TIMP-1 levels showed no difference between the two groups regardless of the presence or absence of intraplaque hemorrhage. No significant differences in MMP levels were observed between symptomatic and asymptomatic patients. Increased levels of MMPs, particularly MMP-9, have been implicated in carotid intraplaque hemorrhage without their serum levels being predictive of local events.