Studies on oxidized low density lipoproteins. Controlled oxidation and a prostaglandin artifact

Low density lipoproteins (LDL), isolated by ultra- centrifugal flotation, were oxidized (LDLoxID) slowly during dialysis against 0.15 M NaCl and subsequent incubation in 96% air-4% C02 at 37OC. Butylated hydroxytoluene prevented LDL oxidation. LDL preparations from different sera were oxidized at different rates and the degree of lipid peroxidation was con- trolled by varying the incubation time. Mild oxidation did not alter the electrophoretic mobility of the LDL~xID preparation. LDLOXID contained lipid peroxides in neutral lipids, had in- creased amounts of lysophosphatidylcholine, and contained a number of complex oxidation products that were generated from the oxidation of free fatty acids. These oxidation products in- cluded large amounts of soluble material that cross-reacted with antibodies to PGE, but not 6-keto-PGF1,. The amount of cross-reacting material was proportional to the degree of lipid peroxidation. Cross-reacting material in LDL~xID prepara- tions was evidently formed from the oxidation of free fatty acids released from LDL, since cross-reacting material was also formed when a synthetic fat emulsion was oxidized in the presence of free arachidonic acid.-Zhang, H., W. B. Davis, X. Chen, R. L. Whisler, and D. G. Cornwell. Studies on oxi- dized low density lipoproteins. Controlled oxidation and a prostaglandin artifact. J Lipid Res. 1989. 30: 141-148. number of studies describe specific effects of oxidized low density lipoproteins (LDL~~ID) that may be related to atherosclerosis. LDL~~ID are taken up by the scavenger receptor of the monocyte/macrophage and degraded by these cells more rapidly than native LDL (II-Zl), We have recently begun a series of studies (22) with LDL~~ID that were prepared by controlled mild oxida- tion. The LDL~~~D preparations were characterized by differences in lipid peroxide content that were measured as thiobarbituric acid reactants (TBAR). LDLo~ID ap- parently contained lipid oxidation products with cross- reactivity in the radioimmunoassay (RIA) of prostanoids. Studies on the formation and properties of LDLOXID and an oxidized synthetic fat emulsion Intralipid@ (11) are presented in this report.