HIGH-DENSITY-LIPOPROTEIN LOSES ITS EFFECT TO STIMULATE EFFLUX OF CHOLESTEROL FROM FOAM CELLS AFTER OXIDATIVE MODIFICATION

In this study, we performed oxidative modification of high density lipoprotein (HDL) in vitro. The amount of lipid peroxide increased when either HDL2 or HDL3 was incubated with phosphate-buffered saline containing 5-mu-M CuSO4 for 24 h at 37-degrees-C, indicating that both fractions of HDL were oxidatively modified. This modification resulted in denaturation of apolipoprotein AI on SDS/PAGE and increased the negative charge on agarose gel electrophoresis. When incubated with macrophage-derived foam cells, native HDL caused a marked efflux of cholesterol from them, leading to a decrease in the amount of cholesteryl ester in the cells. However, oxidized HDL showed a lessened effect on the decrease of cholesteryl ester in foam cells. These data suggest that oxidative modification of HDL may stimulate development of atherosclerosis by limiting efflux of cholesterol from foam cells.