Low density lipoprotein interaction with artery derived proteoglycan: the influence of LDL particle size and the relationship to atherosclerosis susceptibility

Abstract

An in vitro binding system was used to determine whether increases in LDL particle size and altered LDL chemical composition accompanying increased plasma cholesterol concentrations result in greater association of LDL with artery proteoglycan (PG) and whether the binding is related to atherosclerosis. LDL isolated from hypercholesterolemic atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons was complexed to purified White Carneau pigeon aorta-derived high molecular weight PG under conditions whereby PG monomers were saturated. Using LDL of molecular weight > 5.0 × 10 6 daltons from both pigeon breeds, an inverse correlation between LDL size and the number of LDL particles bound per μG PG was demonstrated ( r = 0.87, P < 0.01). This relationship was attributed to the increased size of the LDL particle rather than any modification in chemical composition known to occur when LDL size increases, suggesting the major effect was attributed to steric hindrance. White Carneau pigeons with high molecular weight LDL had more severe atherosclerosis and the PG-LDL complexes contained excess cholesterol but no relationship was seen between atherosclerosis and number of LDL complexed. In animals with LDL between 3.6 × 106 and 4.8 × 106 daltons, considerable variability in PG binding was apparent, but this also was not related to LDL chemical composition. In this group of pigeons, which were all White Carneau, the positive relationship of PG-LDL binding and aorta cholesterol concentration was significant ( r = 0.67, P < 0.05). These results suggest that factors other than chemical composition (perhaps surface charge or apoprotein conformation changes) influence PG-LDL binding and that the assessment of PG-LDL binding is useful in predicting atherosclerosis in animals that do not respond to hypercholesterolemia by increasing LDL size.