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(Stroke. 2004;35:1310.)
© 2004 American Heart Association, Inc.

Original Contributions

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 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.

Correspondence to Shu Ye, Human Genetics Division, School of Medicine, University of Southampton, Duthie Building (808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. 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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