OXIDATION OF LOW-DENSITY LIPOPROTEINS - EFFECT OF ANTIOXIDANT CONTENT, FATTY-ACID COMPOSITION AND INTRINSIC PHOSPHOLIPASE-ACTIVITY ON SUSCEPTIBILITY TO METAL ION-INDUCED OXIDATION

The oxidative modification of low-density lipoprotein (LDL) may play a n important role in atherogenesis. Our understanding of the mechanism of LDL oxidation and the factors that determine its susceptibility to oxidation is still incomplete. We have isolated LDL from 45 healthy in dividuals and studied the relationship between LDL fatty acid, vitamin E and beta-carotene composition, intrinsic phospholipase A(2)-like ac tivity and parameters of LDL oxidation. LDL was exposed to a copper io n-dependent oxidising system and the kinetics of oxidation studied by monitoring formation of fatty acid conjugated dienes. The length of th e lag phase of inhibited lipid peroxidation was measured as well as th e rate of lipid peroxidation during the propagation phase. There was n o significant correlation between LDL antioxidant vitamin or fatty aci d composition and lag time to LDL oxidation. Oleic acid was negatively correlated with the rate of LDL oxidation (r = -0.41, P < 0.01) whils t linoleic acid was significantly correlated with the extent of LDL ox idation measured by the production of total dienes (r = 0.34, P < 0.05 ). Interestingly, LDL vitamin E content was positively correlated with both the rate (r = 0.28, P < 0.05) and extent of LDL oxidation (r = 0 .43, P < 0.01). LDL isolated from this group of subjects showed signif icant intrinsic phospholipase-like activity. The phospholipase activit y, whilst not correlated with lag time, was significantly correlated w ith both rate (r = 0.43, P < 0.01) and total diene production (r = 0.4 4, P < 0.01) of LDL oxidation. We conclude that antioxidant content, f atty acid composition and intrinsic phospholipase activity have little influence on the lag time of Cu-induced LDL oxidation. These componen ts do however, significantly influence both the rate and extent of LDL oxidation, with increased vitamin E, linoleic acid content and phosph olipase activity associated with faster and more extensive oxidation. The possible pro-oxidant effect of vitamin E has interesting implicati ons for the postulated 'protective' effects of vitamin E on atherogene sis.