1-ACYL-2 ACETYL-SN-GLYCERO-3 PHOSPHOCHOLINE DECREASES THE SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN TO OXIDATIVE MODIFICATION BY COPPER IONS, MONOCYTES OR ENDOTHELIAL-CELLS

The effects of platelet-activating factor (PAF) and its analogue, 1 ac yl-2 acetyl-sn-glycero-3 phosphocholine (1 acyl-2 acetyl-GPC), were in vestigated on the oxidative modification of low-density lipoprotein (L DL) by copper ions, U937 monocyte-like cells or endothelial cells, by determination of the lipid peroxidation end products (TBARS) content a nd measurement of the electrophoretic mobility of the particle. 1 Acyl -2 acetyl-GPC, in the concentration range 1-5 mu g/ml, inhibited LDL o xidation in a dose-dependent manner in the three systems, whereas PAF had no effect. The protective effect of 1 acyl-2 acetyl-GPC was marked ly more important when oxidative modification was performed with endot helial cells, leading to total inhibition at 5 mu g/ml. At the same co ncentration, the TBARS production was inhibited by 60% and 20% with mo nocytes and copper ions, respectively. The degradation by J774 macroph age-like cells of LDL modified by copper ions, U937 monocyte-like cell s or endothelial cells was also inhibited when modification was perfor med in the presence of 1 acyl-2 acetyl-GPC. Furthermore, preincubation of the LDL particle with 1 acyl-2 acetyl-GPC before modification prot ected the lipoprotein against oxidation, whereas preincubation of the cultured cells with the phospholipid had no effect. Thus 1 acyl-2 acet yl-GPC decreases the susceptibility of the LDL particle to oxidative m odification, possibly by intercalation within the lipid phase of the p article. Since LDL oxidation is believed to play an important role in the initiation and progression of atherosclerosis, this inhibitory eff ect of 1 acyl-2 acetyl-GPC might be of importance in view of the fact that this phospholipid is produced concomitantly with PAF in some infl ammatory cells.