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(Stroke. 2006;37:235.)
© 2006 American Heart Association, Inc.

Research Reports

Matrix Metalloproteinase 2 Is Associated With Stable and Matrix Metalloproteinases 8 and 9 With Vulnerable Carotid Atherosclerotic Lesions

A Study in Human Endarterectomy Specimen Pointing to a Role for Different Extracellular Matrix Metalloproteinase Inducer Glycosylation Forms

Joost P.G. Sluijter, PhD; Wilco P.C. Pulskens, MSc; Arjan H. Schoneveld, BSc; Evelyn Velema, BSc; Chaylendra F. Strijder, BSc; Frans Moll, MD; Jean-Paul de Vries, MD; Jan Verheijen, PhD, MD; Roeland Hanemaaijer, MD; Dominique P.V. de Kleijn, PhD Gerard Pasterkamp, PhD, MD

From the Experimental Cardiology Laboratory (J.P.G.S., W.P.C.P., A.H.S., E.V., C.F.S., D.P.V.d.K., G.P.) and Vascular Surgery (F.M.), University Medical Center, Utrecht; Interuniversity Cardiology Institute of the Netherlands (J.P.G.S., A.H.S., D.P.V.d.K.), Utrecht; Vascular Surgery (J.P.d.V.), Nieuwegein; and Biomedical Research (J.V., R.H.), The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands.

Correspondence to Gerard Pasterkamp, MD, PhD, University Medical Center, Experimental Cardiology Laboratory, Heidelberglaan 100, Room G02-523, 3584 CX Utrecht, the Netherlands. E-mail g.pasterkamp{at}hli.azu.nl

Background and Purpose— We studied matrix metalloproteinases (MMP) 2, 8, and 9 and extracellular matrix metalloproteinase inducer (EMMPRIN) levels in relation to carotid atherosclerotic plaque characteristics.

Methods— Carotid atherosclerotic plaques (n=150) were stained and analyzed for the presence of collagen, smooth muscle cell (SMC), and macrophages. Adjacent segments were used to isolate total protein to assess MMP-2 and MMP-9 activities and gelatin breakdown, MMP-8 activity, and EMMPRIN levels.

Results— Macrophage-rich lesions revealed higher MMP-8 and MMP-9 activities, whereas SMC-rich lesions showed higher MMP-2 activity. The levels of less glycosylated EMMPRIN-45kD were higher in SMC-rich lesions and lower in macrophage-rich plaques. EMMPRIN-45kD was associated with MMP-2 levels, whereas EMMPRIN-58kD was related to MMP-9 levels.

Conclusions— MMP-2, MMP-8, and MMP-9 activities differed among carotid plaque phenotypes. Different EMMPRIN glycosylation forms are associated with either MMP-2 or MMP-9 activity, which suggests that EMMPRIN glycosylation may play a role in MMP regulation and plaque destabilization.

Key Words: atherosclerosis • carotid arteries • carotid artery plaque • endarterectomy • inflammation • matrix metalloproteinases

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