Published Online
on April 8, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on October 23, 2003
Revised on January 20, 2004
Accepted on February 13, 2004

Differences in Matrix Metalloproteinase-1 and Matrix Metalloproteinase-12 Transcript Levels Among Carotid Atherosclerotic Plaques with Different Histopathological Characteristics

Angharad R. Morgan BSc; Kittipan Rerkasem MD; Patrick J. Gallagher MD, PhD, FRCP; Baiping Zhang DPhil; Gareth E. Morris DM, FRCS; Philip C. Calder PhD; Robert F. Grimble PhD; Per Eriksson PhD; William L. McPheat PhD; Clifford P. Shearman MS FRCS; and Shu Ye MD, PhD^*

From Human Genetics Division (A.R.M., B.Z., S.Y.), Department of Pathology (P.J.G.), Institute of Human Nutrition (P.C.C., R.F.G.), School of Medicine, University of Southampton, UK; Department of Vascular Surgery (K.R., G.E.M., C.P.S.), Southampton General Hospital, UK; Atherosclerosis Research Unit (P.E.), Karolinska Hospital, Sweden; Molecular Pharmacology (W.L.M.), AstraZeneca, Mölndal, Sweden; Department of Surgery (K.R.), Faculty of Medicine, Chiang Mai University, Thailand.

^* To whom correspondence should be addressed. E-mail: Shu.Ye{at}soton.ac.uk.

Background and Purpose--Previous studies have shown that atherosclerotic lesions express a number of matrix metalloproteinases (MMPs). Here we investigated whether transcript levels of MMP-1, -3, -7, -9, and -12 in carotid atherosclerotic plaques were correlated with histological features and clinical manifestations.

Methods--Atherosclerotic plaques (n=50) removed from patients undergoing carotid endarterectomy were classified histologically using a system proposed by Virmani et al, and MMP-1, -3, -7, -9, and -12 transcript levels in these tissues were quantified by real-time reverse-transcriptase polymerase chain reaction.

Results--Compared to plaques with a thick fibrous cap, those with a thin cap had a 7.8-fold higher MMP-1 transcript level (P=0.006). MMP-3, -7, and -12 were 1.5-fold, 1.8-fold, and 2.1-fold, respectively, higher in thin cap plaques, but the differences did not reach statistical significance. MMP-12 transcript levels were significantly increased in ruptured plaques compared with lesions without cap disruption (P=0.001). MMP-9 transcript levels were similar among the different types of lesion. MMP-1 and -12 transcript levels were significantly higher in plaques from patients with amaurosis fugax, than in those from asymptomatic patients (P=0.029 and P=0.008 for MMP-1 and MMP-12, respectively), than in those from patients with stroke (P=0.027 and P=0.001, respectively), and than in those from patients with transient ischemic attack (P=0.046 and P=0.008, respectively).

Conclusions--These data support a role of MMP-1 and -12 in determining atherosclerotic plaque stability.

Key words: carotid arteries • atherosclerosis • metalloproteinases • gene expression

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