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Papers In Press, published online ahead of print September 1, 2002
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Submitted on August 13, 2002
Medicine, University of Washington, Seattle, WA 98195-6426
Corresponding Author: achait{at}u.washington.edu
Retention of apolipoprotein (apo) B and E-containing lipoproteins by extracellular vascular proteoglycans is a critical step in atherogenesis. In addition, high circulating levels of apo C-III are associated with increased atherosclerosis risk. To test whether apo C-III content of apo B-containing lipoproteins affects their ability to bind to the vascular proteoglycan, biglycan, we evaluated the impact of apo C-III on the interaction of [35S]SO4-biglycan derived from cultured arterial smooth muscle cells with lipoproteins obtained from individuals across a spectrum of lipid concentrations. Using an electrophoretic gel-mobility shift assay, low density lipoproteins (LDL) had the highest affinity for biglycan, followed by intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL). The extent of biglycan binding correlated positively with the amount of apo C-III within VLDL (r=0.78, p<0.01), IDL (r=0.67, p<0.01) and LDL (r=0.52, p<0.05). Moreover, the biglycan binding of VLDL, IDL, and LDL was reduced after depletion of apo C-III-containing lipoprotein particles in plasma by anti-apo C-III immunoaffinity chromatography. Since apo C-III does not bind biglycan directly, the enhanced biglycan binding may result from a conformational change associated with increased apo C-III content by which apo B and/or E become more accessible to proteoglycans. This may be an intrinsic property of lipoproteins, since exogenous apo C-III enrichment of LDL and VLDL did not increase binding. Apo C-III content may thus be a marker for lipoproteins that are characterized as having an increased ability to bind proteoglycans.
Revised on September 1, 2002
Accepted on August 20, 2002
Apo C-III Content of Apo B-Containing Lipoproteins is Associated with Binding to the Vascular Proteoglycan, Biglycan
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