Modification of Low Density Lipoprotein Subfractions Separated from Rabbit Hypercholesterolemic Serum

Abstract

Low density lipoprotein (LDL) subfractions, LDL-1, LDL-2, and LDL-3, separated from rabbit hypercholesterolemic serum and normal LDL from normal rabbit serum were modified by exposure to air in the absence or presence of Cu²⁺ at 37°C. When these LDLs were incubated in the presence of Cu²⁺, the lipid peroxide level and the mobility in agarose gel electrophoresis were increased in the following order: LDL-1>LDL-2>LDL-3>normal LDL. In the absence of Cu²⁺, the increases were also remarkable for LDL-1, less for LDL-2, but nonexistent for LDL-3 and normal LDL. Incubation in the presence of Cu²⁺ brought about the degradation of apo B-100 and the formation of fluorescent substances in these samples, but such did not occur in the absence of Cu²⁺. LDL samples modified in the presence of Cu²⁺ were taken up by rat peritoneal macrophages to the following extents: LDL-1>LDL-2>LDL-3>normal LDL. This tendency was supported by fluorescence microscopic observation using 1, 1′-dioctadecyl 3, 3, 3′, 3′-tetra-methylindocarbocyanine perchloride-labeled samples, and by the contents of total cholesterol in macrophages. These results indicate that LDL-1, which was identified as the main component of intermediate density lipoprotein, is more susceptible to lipid peroxidation-mediated modification and is more atherogenic than other subfractions of LDL.