Quantitation and localization of matrix metalloproteinases and their inhibitors in human carotid endarterectomy tissues. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a central role in arterial wall remodeling, affecting stability of fibrous caps covering atherosclerotic plaques. The objective of this study was to determine the spatial distribution of TIMP mass and MMP mass and activity of carotid endarterectomy (CEA) tissues and relate it to the distribution of atherosclerotic lesions. METHODS AND RESULTS: Fresh CEA tissues were imaged by multicontrast MRI to generate 3D reconstructions. Tissue segments were cut transversely from the common, bifurcation, internal, and external regions. Segments were subjected to total protein extractions and analyzed by ELISA for MMP-2 and -9 and TIMP-1 and -2 mass and by zymography for gelatinase activity. Segments at or near the bifurcation with highly calcified lesions contained higher MMP levels and activity than segments distant from the bifurcation; highly fibrotic or necrotic plaque contained lower MMP levels and activity and higher TIMP levels. Fatty streak, fibroatheroma with hemorrhage and calcification, and fully occluded lesions were enriched in MMP-2, MMP-9, and TIMP-1 and TIMP-2, respectively. CONCLUSIONS: The spatial distribution of MMPs and TIMPs in carotid atherosclerotic lesions is highly heterogeneous, reflecting lesion location, size, and composition. This study provides the first semi-quantitative maps of differential distribution of MMPs and TIMPs over atherosclerotic plaques.

publication date

  • August 3, 2006

Research

keywords

  • Carotid Arteries
  • Endarterectomy, Carotid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2

Identity

Scopus Document Identifier

  • 33749074726

PubMed ID

  • 16888239

Additional Document Info

volume

  • 26

issue

  • 10