Published Online
on December 8, 2005

A more recent version of this article appeared on January 1, 2006

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Submitted on August 17, 2005
Revised on October 6, 2005
Accepted on October 21, 2005

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; and 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.

^* To whom correspondence should be addressed. 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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