Quantitation and localization of matrix metalloproteinases and their inhibitors in human carotid endarterectomy tissues

Salman Choudhary, Catherine L. Higgins, Iou Yih Chen, Michael Reardon, Gerald Lawrie, G. Wesley Vick, Christof Karmonik, David P. Via, Joel D. Morrisett

Research output: Contribution to journalArticle

75 Scopus citations

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. CONCLUSION - 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.

Original languageEnglish (US)
Pages (from-to)2351-2358
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number10
DOIs
StatePublished - Oct 2006

Keywords

  • Atherosclerosis
  • Carotid artery
  • MMPs
  • MRI
  • TIMPs

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Quantitation and localization of matrix metalloproteinases and their inhibitors in human carotid endarterectomy tissues'. Together they form a unique fingerprint.

Cite this