Integrin and Matrix Metalloproteinase Expression in Human Carotid Plaque

Carlos A. Murillo, Kenneth J. Woodside, Qian Guo, Shu Zhang, Kathleen L. O'Connor, Glenn C. Hunter

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: Neointimal thickening is the major cause of restenosis after carotid endarterectomy (CEA) and carotid stenting. The biologic behavior of these lesions is regulated by the interaction between smooth muscle cells (SMCs), endothelial cells (ECs), and extracellular matrix (ECM) proteins. Although the contribution of the cellular components of neointimal lesions has been extensively studied, the role of the ECM proteins in lesion remodeling is less well defined. Methods: We examined primary and restenotic carotid endarterectomy specimens to determine their cellular morphology. Tissue was also preserved for protein extraction for Western immunoblotting and mRNA for RT-PCR and cDNA microarray analysis. Results: All primary lesions demonstrated the features of complex atherosclerotic plaque. Restenotic lesions were composed of SMCs embedded in ECM. Microarray analysis demonstrated altered expression of 13 of 96 genes. Eight genes were increased more than 3-fold and five genes were decreased more than 3-fold in primary plaque compared with restenotic lesions. RT-PCR confirmed α2-, α6-, and β3-integrin gene expression in reference tissue, primary plaque, and restenotic lesions, with the greatest expression in primary plaque. Primary plaque demonstrated increased protein expression of plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase (TIMP-1). By zymography, pro-MMP-2, pro-MMP-9 levels, and MMP-2 activity were also increased in primary plaque compared with reference and restenotic tissues. Conclusions: The decreased integrin expression and protease activity in restenotic lesions versus primary carotid plaques suggests that the neointimal lesions were in a quiescent phase. These alterations in protein expression and protease activity demonstrate the importance of proteinase/inhibitor imbalance in regulating plaque remodeling.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalJournal of Surgical Research
Volume155
Issue number1
DOIs
StatePublished - Jul 2009

Bibliographical note

Funding Information:
This work was supported in part by a grant-in-aid (no. 0255736Y) from the Texas Chapter of the American Heart Association.

Keywords

  • atherosclerosis
  • cDNA gene array
  • carotid endarterectomy
  • carotid restenosis
  • carotid stenosis
  • extracellular matrix
  • human tissue
  • integrins
  • matrix metalloproteinases

ASJC Scopus subject areas

  • Surgery

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