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

Authors :
Choudhary S
Higgins CL
Chen IY
Reardon M
Lawrie G
Vick GW 3rd
Karmonik C
Via DP
Morrisett JD
Source :
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2006 Oct; Vol. 26 (10), pp. 2351-8. Date of Electronic Publication: 2006 Aug 03.
Publication Year :
2006

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.<br />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.<br />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.

Details

Language :
English
ISSN :
1524-4636
Volume :
26
Issue :
10
Database :
MEDLINE
Journal :
Arteriosclerosis, thrombosis, and vascular biology
Publication Type :
Academic Journal
Accession number :
16888239
Full Text :
https://doi.org/10.1161/01.ATV.0000239461.87113.0b