Low density lipoprotein uptake: holoparticle and cholesteryl ester selective uptake

Low density lipoproteins (LDL) contain apolipoprotein B-100 and are cholest eryl eater-rich, triglyceride-poor macromolecules, arising from the lipolys is of very low density lipoproteins. This review will describe the receptor s responsible for uptake of whole LDL particles (holoparticle uptake), and the selective uptake of LDL cholesteryl ester. The LDL-receptor mediates th e internalization of whole LDL through an endosomal-lysosomal pathway, lead ing to complete degradation of LDL, Increasing LDL-receptor expression by p harmacological intervention efficiently reduces blood LDL concentrations. T he lipolysis stimulated receptor and LDL-receptor related protein may also lead to complete degradation of LDL in presence of free fatty acids and apo lipoprotein E- or lipase-LDL complexes, respectively. Selective uptake of L DL cholesteryl eater has been demonstrated in the liver, especially in rode nts and humans. This activity brings five times more LDL cholesteryl eater than the LDL-receptor to human hepatoma cells, suggesting that it is a phys iologically significant pathway. The lipoprotein binding site of HepG2 cell s mediates this process and recognizes all lipoprotein classes. Scavenger r eceptor class B type I and CD36, which mediate the selective uptake of high density lipoprotein cholesteryl eater, are potentially involved in LDL cho lesteryl ester selective uptake, since they both bind LDL with high affinit y. It is not known whether they are identical to the uncloned lipoprotein b inding site and if the selective uptake of LDL cholesteryl ester produces a less atherogenic particle. If this is verified, pharmacological up-regulat ion of LDL cholesteryl ester selective uptake may become another therapeuti c approach for reducing blood LDL-cholesterol levels and the risk of athero sclerosis. (C) 1999 Elsevier Science Ltd. AII rights reserved.