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.
OBJECTIVE
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.
Sluijter
Joost P G
JP
Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands.
Pulskens
Wilco P C
WP
Schoneveld
Arjan H
AH
Velema
Evelyn
E
Strijder
Chaylendra F
CF
Moll
Frans
F
de Vries
Jean-Paul
JP
Verheijen
Jan
J
Hanemaaijer
Roeland
R
de Kleijn
Dominique P V
DP
Pasterkamp
Gerard
G
D000704:Analysis of Variance; D051926:Basigin / Q000502:physiology*; D002340:Carotid Artery Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004691:Endarterectomy / Q000379:methods; D005109:Extracellular Matrix / Q000201:enzymology*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism / Q000502:physiology*; D020784:Matrix Metalloproteinase 8 / Q000737:chemistry*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010641:Phenotype
D051926:Basigin; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9