Stimulating effect of biologically modified low density lipoproteins on ADP-induced aggregation of washed platelets persists in absence of specific binding

Oxidized low density lipoproteins are closely associated with atheroscleros is and also might be directly involved in thrombosis because they have been shown to mediate a stimulating effect on human platelets. In this work, we used biologically modified low density lipoproteins (i.e., low density lip oproteins sufficiently oxidized to show specificity for the macrophage scav enger receptor system) to examine if specific binding of the oxidized apoli poprotein moiety to the platelet surface is a prerequisite for the platelet -stimulating effects reported by other authors. We find that biologically m odified low density lipoproteins show specific binding to human platelets ( K-d = 5.83 +/- 0.4 mu g/mL, 3850 +/- 620 sites/platelet) and strongly augme nt both ADP- and thrombin-induced aggregation of washed platelets. Maleylat ed albumin, an antagonist of oxidized low density lipoproteins binding to a ll currently classified scavenger receptors, is able to reduce platelet oxi dized low density lipoproteins binding to background levels. Nevertheless, maleylated albumin is not able to exert any kind of normalizing effect on t he augmented ADP-induced aggregation response observed in the presence of b iologically modified low density lipoproteins. From these data, we conclude that specific binding of oxidatively modified apolipoprotein B to the plat elet surface is not essential to the process of platelet stimulation. There fore, we conclude that these stimulating effects may be mediated by unident ified compounds formed in the lipid phase of the lipoproteins. (C) 2000 Els evier Science Ltd. All rights reserved.