Circulation Research. 2004;94:1158-1167
doi: 10.1161/01.RES.0000126921.29919.51
doi: 10.1161/01.RES.0000126921.29919.51
© 2004 American Heart Association, Inc.
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Proteoglycans in Atherosclerosis and Restenosis
Key Roles for Versican
From the Department of Vascular Biology (T.N.W.), The Hope Heart Institute, Seattle, Wash; and Department of Anatomy with Radiology (M.J.M.), School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
Correspondence to Thomas N. Wight, Department of Vascular Biology, The Hope Heart Institute, 1124 Columbia St, No. 783, Seattle, WA 98104-2046. E-mail twight{at}hopeheart.org
The proteoglycan versican is one of several extracellular matrix (ECM) molecules that accumulate in lesions of atherosclerosis and restenosis. Its unique structural features create a highly interactive molecule that binds growth factors, enzymes, lipoproteins, and a variety of other ECM components to influence fundamental events involved in vascular disease. Versican is one of the principal genes that is upregulated after vascular injury and is a prominent component in stented and nonstented restenotic lesions. The synthesis of versican is highly regulated by specific growth factors and cytokines and the principal source of versican is the smooth muscle cell. Versican interacts with hyaluronan, a long chain glycosaminoglycan, to create expanded viscoelastic pericellular matrices that are required for arterial smooth muscle cell (ASMC) proliferation and migration. Versican is also prominent in advanced lesions of atherosclerosis, at the borders of lipid-filled necrotic cores as well as at the plaque-thrombus interface, suggesting roles in lipid accumulation, inflammation, and thrombosis. Versican influences the assembly of ECM and controls elastic fiber fibrillogenesis, which is of fundamental importance in ECM remodeling during vascular disease. Collectively, these studies highlight the critical importance of this specific ECM component in atherosclerosis and restenosis.
Key Words: proteoglycans • versican • extracellular matrix • atherosclerosis • smooth muscle cells
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