MODIFICATION OF LOW-DENSITY-LIPOPROTEIN SUBFRACTIONS SEPARATED FROM RABBIT HYPERCHOLESTEROLEMIC SERUM

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-degrees-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'-tetramethylindocarbocyanine 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.