J Clin Neurol.  2011 Jun;7(2):69-76. 10.3988/jcn.2011.7.2.69.

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

• Heo SH
• Cho CH
• Kim HO
• Jo YH
• Yoon KS
• Lee JH
• Park JC
• Park KC
• Ahn TB
• Chung KC
• Yoon SS
• Chang DI

• KMID: 2178969
• DOI: http://doi.org/10.3988/jcn.2011.7.2.69

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.

Keyword

metalloproteinase; carotid plaque; instability

MeSH Terms

Atherosclerosis
Carotid Arteries
Carotid Artery Diseases
Endarterectomy, Carotid
Hemorrhage
Humans
Matrix Metalloproteinases
Plaque, Atherosclerotic
Rupture
Stroke
Thromboembolism
Ulcer
Matrix Metalloproteinases

Figure

• 

  Fig. 1 Gross and histological morphology of a carotid specimen. A: Transverse sections were taken at 5-mm intervals and divided into central, shoulder, and peripheral regions. B: Results of hematoxylin and eosin staining (×10). C: Thrombus (×100). D: Rupture (×100). E: Necrotic lipid core (×100).

• 

  Fig. 2 Carotid specimens that were immunohistochemically positive for MMP-2 (A) and MMP-9 (B) were also strongly positive for CD68 (C) but negative for SMA (D). MMP: matrix metalloproteinase, SMA: smooth-muscle actin.

• 

  Fig. 3 Immunofluorescence staining illustrating the expressions of MMP-2 and MMP-9 produced by macrophages in carotid plaques. A and D: MMP-2 and MMP-9 were visualized with secondary antibodies conjugated to Texas Red (red). B and E: The nuclei were stained with DAPI (blue). C and F: MMPs colocalized with the cytoplasm in the macrophages. The white boxes in each image are magnified. Scale bar=100 µm. MMP: matrix metalloproteinase.

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