OXIDATION-INDUCED AGGREGATION OF RABBIT LOW-DENSITY-LIPOPROTEIN BY AZO INITIATOR

Oxidation of low-density lipoprotein (LDL) has been considered as an i mportant step in the early pathogenesis of atherosclerosis. We investi gated the oxidative modification of LDL by a water-soluble azo-initiat or AAPH (2,2,-azo-bis(2-amidinopropane) - 2HCl) and analyzed the uptak e of AAPH-oxidized LDL with mouse peritoneal macrophages. Oxidative mo dification of LDL by AAPH was similar to the modification induced by c opper in regard to the degree of oxidation and formation of aggregated LDL. The aggregated oxidized (AO-) LDL was fractionated by gel permea tion chromatography and compared with the monomeric oxidized (MO-) LDL to make clear their characterization. The results of binding, cell as sociation, and degradation with macrophages indicated that both AO- an d MO-LDL were bound and endocytosed by macrophages. The cross competit ion experiment showed that nonreciprocal competition existed among MO- LDL, AO-LDL, and monomeric acetylated (MAc-) LDL. By the sterol accumu lation experiment in macrophages with the various types of modified LD L, the cellular sterol accumulation was shown as the following order, AO-LDL, MAc-LDL > MO-LDL. These results indicated that the oxidation b y AAPH can induce the aggregation of LDL and that the AO-LDL contribut e to lipid accumulation into macrophages more than the RIO-LDL. (C) 19 94 Academic Press, Inc.