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on August 3, 2006

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006
Published online before print August 3, 2006, doi: 10.1161/01.ATV.0000239461.87113.0b
A more recent version of this article appeared on October 1, 2006
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Submitted on February 27, 2006
Accepted on June 21, 2006

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 III ; Christof Karmonik ; David P. Via ; and Joel D. Morrisett *

From the Departments of Medicine and Biochemistry and Molecular Biology (S.C., C.L.H., I.Y.C., D.P.V., J.D.M.), Baylor College of Medicine; The Methodist Hospital (M.R., G.L.); Department of Pediatrics (G.W.V.), Texas Children’s Hospital; and Department of Radiology (C.K.), The Methodist Hospital Research Institute, Houston, Tex.

* To whom correspondence should be addressed. E-mail: morriset{at}bcm.tmc.edu.

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.
Key words: carotid artery • atherosclerosis • MMPs • TIMPs • MRI


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