Partial structure of the active moiety of a lipoprotein complexing proteoglycan from human aorta.
Proteoglycans and glycosaminoglycans of the intima-media extracellular matrix have been stated to play a role in lipoprotein deposition associated with atherogenesis. It is therefore important to characterize the active lipoprotein-complexing moiety of these macromolecular aggregates. We have isolated a soluble proteoglycan aggregate of approximately 5 X 10(6) molecular weight after homogenization of human aortic intima-media in an isosmotic sucrose solution, sequential differential centrifugation, dialysis, exclusion chromatography and preparative electrophoresis. This proteoglycan aggregate, labelled lipoprotein-complexing proteoglycan (LCP), has been previously shown to form specific complexes with low density lipoproteins, either isolated or in sera. Density gradient centrifugation in dissociative conditions of the LCP, cellulose acetate acetate electrophoresis of the subfractions, chondroitinases treatment and high performance liquid chromatography of the unsaturated disaccharides indicated that the glycosaminoglycan moiety was composed of 56% chondroitin-6-SO4, 26% hyaluronate and/or undersulfated chondroitin and 17% chondroitin-4-SO4. In pore-gradient polyacrylamide gel electrophoresis, the hyaluronate monomer appeared to have a molecular weight of 250000 while that of the chondroitin sulfates ranged between 50000 and 70000 after extensive treatment with protease. The fractions enriched in the chondroitin sulfate monomers were the most reactive towards LDL and their reactivity was abolished by chondroitinase AC indicating that the lipoprotein-complexing capacity of the LCP aggregate is associated to these molecules.
D001011:Aorta / Q000032:analysis*; D002500:Centrifugation, Isopycnic; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D008077:Lipoproteins, LDL / Q000032:analysis*; D008854:Microscopy, Electron; D008970:Molecular Weight; D011509:Proteoglycans / Q000032:analysis*; D013329:Structure-Activity Relationship
D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D011509:Proteoglycans