Lipoprotein lipase enhances the binding of native and oxidized low density lipoproteins to versican and biglycan synthesized by cultured arterial smooth muscle cells.
Retention of low density lipoproteins (LDL) by vascular proteoglycans and their subsequent oxidation are important in atherogenesis. Lipoprotein lipase (LPL) can bind LDL and proteoglycans, although the effect of different proteoglycans to influence the ability of LPL to act as a bridge in the formation of LDL-proteoglycan complexes is unknown. Using an electrophoretic gel mobility shift assay, [(35)S]SO(4)-labeled versican and biglycan, two extracellular proteoglycans secreted by vascular cells, bound native LDL in a saturable fashion. The addition of bovine milk LPL dose-dependently increased the binding of native LDL to both versican and biglycan, approaching saturation at 30-40 microgram/ml LPL for versican and 20 microgram/ml LPL for biglycan. LDL was oxidized by several methods, including copper, 2, 2-azo-bis(2-amidinopropane)-2HCl and hypochlorite. Extensively copper- and hypochlorite-oxidized LDL bound poorly to versican and biglycan. Proteoglycan binding to LDL was correlated inversely with the extent of LDL; however, the addition of LPL to oxidized LDL together with biglycan or versican allowed the oxidized LDL to bind the proteoglycans in an LPL dose-dependent manner. Addition of LPL had a greater relative effect on the binding of extensively oxidized LDL to proteoglycans compared with native LDL. LPL had a slightly greater effect on increasing the binding of native and oxidized LDL to biglycan than versican. Thus, LPL in the artery wall might increase the atherogenicity of oxidized LDL, since it enables its binding to vascular biglycan and versican.
Olin
K L
KL
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
Potter-Perigo
S
S
Barrett
P H
PH
Wight
T N
TN
Chait
A
A
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D058578:Biglycan; D002417:Cattle; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins; D006801:Humans; D007700:Kinetics; D037181:Lectins, C-Type; D008071:Lipoprotein Lipase / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008894:Milk Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism*; D053675:Versicans
C546884:BGN protein, human; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL; D008894:Milk Proteins; D011509:Proteoglycans; C508322:VCAN protein, human; D053675:Versicans; D008071:Lipoprotein Lipase