Competitive inhibition of LDL binding and uptake by HDL in aortic endothelial cells.
High-density lipoprotein (HDL) may inhibit the binding and cellular uptake of low-density lipoprotein (LDL) as one means of regulating the delivery of exogenous cholesterol to nonhepatic tissues. This may play an important role in atherogenesis, by altering lipid metabolism in cells of the arterial wall. To verify and better characterize this effect, endothelial cells were harvested from bovine aorta and maintained in tissue culture. Following initial preincubation in lipid-deficient culture media, these cells were incubated for 2 hr at 4 degrees C in media containing 125I-LDL (10 micrograms protein/ml) and varying concentrations of either HDL (0-400 micrograms protein/ml) or comparable amounts of Apoprotein A (Apo A), the major protein component of HDL. Intracellular and trypsin-released counts were assayed separately, as a measurement of cellular uptake and membrane bound LDL, respectively. Results of this study indicated an inhibition of LDL binding and uptake by HDL (P less than 0.005, ANOVA). A similar inhibition was found with Apo A alone (P less than 0.005). When identical studies were performed using 125I-Apoprotein B, the protein component of LDL, and Apo A, the latter was found to inhibit the binding of Apo B to the same extent (P less than 0.0006). These results indicate that HDL does inhibit LDL binding and uptake by bovine aortic endothelial cells and that, because this effect is seen equally with only the protein component of these lipoprotein particles, it is most likely due to competitive binding at the receptor level rather than to stearic hindrance or an alteration of the cell membrane.
Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Ohio 44109.
J J
JJ
Alexander
R
R
Miguel
D
D
Graham
D000818:Animals; D001011:Aorta; D001054:Apolipoproteins A / Q000494:pharmacology; D001055:Apolipoproteins B / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*
D001054:Apolipoproteins A; D001055:Apolipoproteins B; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL