Plaque Rupture is a Determinant of Vascular Events in Carotid Artery Atherosclerotic Disease: Involvement of Matrix Metalloproteinases 2 and 9

ABSTRACT

BACKGROUND AND PURPOSE: Unstable carotid atherosclerotic plaques are characterized by cap rupture, leading to thromboembolism and stroke. Matrix metalloproteinases (MMPs) have been implicated in the progression of atherosclerosis and plaque rupture. The aim of this study was to assess the relationship between the expressions of MMP-2 and MMP-9 and carotid plaque instability. METHODS: Eighty atherosclerotic plaques were collected from 74 patients undergoing carotid endarterectomy. Clinical information was obtained from each patient, and plaque morphology was examined at the macroscopic and microscopic levels. The immunohistochemical expressions of MMPs were graded using semiquantitative scales. RESULTS: Macroscopic ulceration (84.6% versus 63.4%, p=0.042) and microscopic cap rupture (79.5% versus 51.2%, p=0.010) were more common in symptomatic than in asymptomatic patients. Immunoreactivities of MMP-2 and MMP-9 were increased in 40 and 36 atheromatous plaques, respectively. Macroscopic ulceration was strongly correlated with the expressions of MMP-2 (p<0.001) and MMP-9 (p=0.001). There were significant correlations between increased MMP-2 expression and cap rupture (p=0.002), intraplaque hemorrhage (p=0.039), and a thin fibrous cap (p=0.002), and between increased MMP-9 expression and cap rupture (p=0.010) and a large lipid core (p=0.013). CONCLUSIONS: Plaque rupture was significantly associated with the development of vascular events in carotid atherosclerotic disease. MMP-2 and MMP-9 are strongly correlated with plaque instability.