The effect of oxidatively modified low-density lipoproteins on platelet aggregability and membrane fluidity.
The influence of oxidised low-density lipoproteins (oxLDL) on blood cell functions plays a role in the progression of atherosclerosis. In the present work the effects of mildly oxidised LDL (moxLDL) on platelet aggregability and plasma membrane fluidity were studied and analysed from the viewpoint of the extent of LDL oxidation. Native or oxidised LDL were incubated with platelet rich plasma (PRP) at the volume ratio 1:1. As a control, plasma was incubated with buffer. The effects on ADP-induced platelet aggregation and certain membrane characteristics are described. (1) Mildly oxidised LDL diminished the time-dependent decrease in platelet aggregability that was observed when PRP was incubated with buffer or native LDL. The higher the oxidation extent of moxLDL, the lesser (if any) decrease in platelet activity occurred. Therefore moxLDL activated platelets in PRP. Cu2+-oxidised LDL, characterised by a high extent of lipid oxidation, inhibited ADP-induced platelet aggregation. (2) Comparison of the ESR spectra of spin-labelled fatty acid (5-doxylstearate) incorporated into the plasma membrane of washed platelets indicated that the presence of moxLDL in the incubation medium resulted in a reduced fluidity of the outer membrane layer. The cholesterol:phospholipid ratio in platelets appeared to be the same after PRP incubation with native LDL, moxLDL or buffer. It may be proposed that the binding of oxLDL to the platelet surface leads to a modification of the membrane fluidity, thus mediating the activating action of LDL on platelets. Both effects were proportional to the extent of lipid oxidation in LDL. The results of this paper indicate a crucial role for mildly oxidised LDL in platelet activation.
Vlasova
I I
II
Research Institute for Physical and Chemical Medicine, Moscow, Russia. vvv@m81.ipmce.ru
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D003300:Copper / Q000494:pharmacology; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects*; D010084:Oxidation-Reduction; D010974:Platelet Aggregation / Q000187:drug effects*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D008077:Lipoproteins, LDL; D013113:Spin Labels; C099252:oxidized low density lipoprotein; C005072:5-doxylstearic acid; D000244:Adenosine Diphosphate; D003300:Copper