Effect of Exogenous Apo E on the Cellular Binding of Lipoproteins

It is well known that apolipoprotein E (apo E) has a significant role in the metabolism of plasma cholesterol through receptor-mediated endocytosis of lipoproteins containing apo B 100. We have reported that intravenous administration of apo E increases the clearance of lipoproteins containing apo B 100, resulting in reduced plasma cholesterol levels in WHHL rabbits. In the present study, we investigated the effects of exogenous apo E on lipoprotein binding to cell surface receptors. Lipoproteins were enriched in apo E by the incubation with purified apo E. Among lipoproteins enriched in apo E, VLDL and intermediate-density lipoprotein demonstrated higher binding affinity to cell surface receptor on fibroblast than respective unmodified lipoproteins. In competitive binding study, VLDL enriched by apo E (VLDL+E) completely suppressed 125I-LDL binding to human skin fibro-blasts and showed the greatest binding activity among different lipoprotein classes, whereas both VLDL and LDL incompletely suppressed a binding of 125I-VLDL+E. This result indicated that apo-E-rich VLDL can bind not only to LDL receptor but to binding sites other than LDL receptors.