Platelet activation by oxidatively modified low density lipoproteins.
Interactions between altered lipoproteins and platelets may be important in atherosclerosis lesion formation and thrombosis. The aims of this study were to compare the effects of oxidatively modified and native low density lipoproteins (LDL) and high density lipoproteins (HDL) on platelet responses in the presence and absence of other platelet agonists, and investigate the mechanism(s) by which lipoproteins influence platelet activation. We have shown that native and oxidatively modified lipoproteins differ importantly in their effects on platelets; oxidation renders lipoproteins more reactive to platelets. Native LDL promote aggregation of human platelets, enhance the mobilization of arachidonate from phospholipids, increase thromboxane B2 production, and decrease membrane fluidity. Oxidized LDL are more reactive than native LDL and alone cause aggregation. Native HDL inhibit platelet responses and increase membrane fluidity. Oxidized HDL promote aggregation and cause spontaneous aggregation. The enhanced platelet responses cannot be attributed to increased production of thromboxane A2 since cyclooxygenase inhibitors (aspirin, indomethacin) have little inhibitory effect. The data suggest that activation of platelets by lipoproteins results from changes in membrane fluidity. These observations shed new light on the potential role of altered lipoproteins in the pathogenesis of atherosclerosis and its complications.
Ardlie
N G
NG
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra.
Selley
M L
ML
Simons
L A
LA
D001095:Arachidonic Acids / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D010084:Oxidation-Reduction; D010740:Phospholipases / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*
D001095:Arachidonic Acids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010740:Phospholipases