Recognition Sites on Rat Liver Cells for Oxidatively Modified /3-Very Low Density Lipoproteins

The in vivo fate of /3-very low density lipoproteins (0-VLDLs) was investigated after Cu-mediated oxidative modification (Ox-0-VLDL). Ox-0-VLDL may be physiologically relevant under conditions of defective VLDL removal by the liver (type HI hyperlipoproteinemia) or overloading of the remnant receptor (high cholesterol feeding). On oxidation of /3 -VLDL, the kinetics of its removal from the blood and uptake by the liver are unchanged. However, in contrast to /3-VLDL, which is recognized by the remnant receptor of parenchymal cells, liver uptake of Ox-^-VLDL is mediated mainly by Kupffer cells (65% of liver-associated radioactivity). In vitro competition studies show that the cell association and degradation of iodine-125-labeled Ox-fi -VLDL by both liver endothelial and Kupffer cells are only marginally competed for by acetylated LDL (10-20%), while an efficient blockade is noted with Ox-/3VLDL, oxidized low density lipoproteins, or polyinosinic acid (80-90%). The capacity of Kupffer cells to associate with and degrade I-Ox-/3-VLDL appears to be twofold higher than for endothelial cells. It is concluded that on oxidation of /3-VLDL, the recognition system responsible for the uptake of fi-VLDL from the blood circulation is shifted from the remnant receptor to a specific oxidized-lipoprotein receptor. The efficiency of the scavenger activity on Kupffer cells will then form the protection system against the prolonged circulation of these atherogenic lipoproteins in the blood. (Arteriosclerosis and Thrombosis 1992;12:41-49)