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 atherosclerosis 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 lipoproteins sufficiently oxidized to show specificity for the macrophage scavenger receptor system) to examine if specific binding of the oxidized apolipoprotein moiety to the platelet surface is a prerequisite for the platelet-stimulating effects reported by other authors. We find that biologically modified low density lipoproteins show specific binding to human platelets (K(d)=5.83+/-0.4 microg/mL, 3850+/-620 sites/platelet) and strongly augment both ADP- and thrombin-induced aggregation of washed platelets. Maleylated albumin, an antagonist of oxidized low density lipoproteins binding to all currently classified scavenger receptors, is able to reduce platelet oxidized low density lipoproteins binding to background levels. Nevertheless, maleylated albumin is not able to exert any kind of normalizing effect on the augmented ADP-induced aggregation response observed in the presence of biologically modified low density lipoproteins. From these data, we conclude that specific binding of oxidatively modified apolipoprotein B to the platelet surface is not essential to the process of platelet stimulation. Therefore, we conclude that these stimulating effects may be mediated by unidentified compounds formed in the lipid phase of the lipoproteins.
Volf
I
I
Institute of Medical Physiology, Schwarzspanierstr. 17 A-1090, Vienna, Austria. ivo.volf@univie.ac.at
Roth
A
A
Moeslinger
T
T
Cooper
J
J
Schmid
W
W
Zehetgruber
M
M
Koller
E
E
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D002460:Cell Line; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D012710:Serum Albumin, Bovine; D000244:Adenosine Diphosphate; D013917:Thrombin