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

Stroke. 2006 Jan;37(1):235-9. doi: 10.1161/01.STR.0000196986.50059.e0. Epub 2005 Dec 8.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Basigin / physiology*
  • Carotid Artery Diseases / genetics
  • Carotid Artery Diseases / metabolism*
  • Carotid Artery Diseases / pathology
  • Cell Line
  • Collagen / metabolism
  • Endarterectomy / methods
  • Extracellular Matrix / enzymology*
  • Glycosylation
  • Humans
  • Immunohistochemistry
  • Inflammation
  • Macrophages / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 2 / physiology*
  • Matrix Metalloproteinase 8 / chemistry*
  • Matrix Metalloproteinase 9 / chemistry*
  • Matrix Metalloproteinase 9 / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Phenotype

Substances

  • Basigin
  • Collagen
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9