In vivo catabolism of biologically modified LDL

Abstract

Incubation of human low density lipoprotein (LDL) at 37°C in the presence of human umbilical vein endothelial cells (EC) caused a time-dependent shift in the charge and density of LDL. The physical changes of the human LDL occurred parallel with an increase in its clearance from the serum and uptake in the liver when injected into rats. The serum decay of the EC-modified LDL (44 hours incubation) was 20 times faster than for control LDL. EC-modified LDL, cleared from the blood, was quantitatively recovered in the liver. Isolation of the different liver cell types (parenchymal, Kupffer, and endothelial cells) after in vivo injection of 125I-EC-modified LDL showed that approximately 30 times more radioactivity was associated with the endothelial cells than with the parenchymal cells (per milligram of cell protein). In vitro experiments indicated that EC-modified-LDL was processed by the rat liver endothelial cells via a high affinity, saturable pathway related to the pathway by which these cells processed acetyl-LDL. We concluded that, if EC-modified LDL is generated in vivo, the liver, and in particular the endothelial cell, forms the major protection system against the occurrence of atherogenic particles in the blood.