Y. Kawabe et al., OXIDATION-INDUCED AGGREGATION OF RABBIT LOW-DENSITY-LIPOPROTEIN BY AZO INITIATOR, Archives of biochemistry and biophysics, 310(2), 1994, pp. 489-496
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.