chondroitin-sulfates and cholesteryl-oleate

Proteoglycans are considered to facilitate lipid accumulation in the arterial wall, as part of the injury and repair process in atherogenesis. The present study determined (1) characteristics of arterial tissue chondroitin sulfate proteoglycan (CS-PG) monomers of versican type that vary in binding affinity to low-density lipoproteins (LDL), and (2) the ability of these variants to modulate LDL metabolism by macrophages. A large CS-PG devoid of dermatan sulfate (DS) was isolated and purified from bovine aorta intima-media under dissociative conditions. The proteoglycan was further subfractionated by LDL affinity chromatography into CS-PGI and CS-PGII variants, the former eluting at 0.1 M NaCl and the latter at 1.0 M NaCl. The core protein of both variants had a similar molecular mass (1.7 x 10(5). However, CS-PGII contained more glycosaminoglycan (GAG) chains (30 vs. 25) with higher average molecular mass (4.2 x 10(4) vs. 3.8 x 10(4)) than CS-PGI. Furthermore, CS-PGII contained a relatively higher proportion of CS6-sulfate to CS4-sulfate (65: 35 vs. 52: 48). Sulfate-to-hexosamine molar ratio of GAG measured approximately 1 in both variants. In terms of metabolism by macrophages, when compared to complex of LDL and CS-PGI, complex of LDL and CS-PGII produced consistent increase in degradation (10.3-fold vs. 8.4-fold over native LDL) and cell association (16.3-fold vs. 10.2-fold over native LDL) of the ligand, and stimulation of cholesteryl ester synthesis (8.4-fold vs. 6.4-fold over native LDL). CS-PGII was as potent as native CS/DS-PG aggregate, which is a complex made of proteoglycan monomers, hyaluronate, and link protein(s), in stimulating the above activities in macrophages. Thus, variations in LDL-binding affinity of CS-PG can potentially modulate the lipid accumulation in atherogenesis.

Topics: Amino Acids; Animals; Aorta; Cattle; Cell Line; Cholesterol Esters; Cholesterol, LDL; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Glycosaminoglycans; Humans; Lectins, C-Type; Lipoproteins, LDL; Macrophages; Molecular Weight; Receptors, LDL; Versicans