The role of lipoprotein receptors in lipid transport and in the pathogenesis of the hyperlipoproteinemias.

Three distinct classes of receptors for lipoproteins exist. The best studied is the LDL receptor, the primary function of which is the delivery of cholesterol in response to cellular needs. Although originally thought to be specific for LDL, it clearly recognizes lipoproteins that contain either apo B or E. It plays an important role in the catabolism of LDL and could also be involved in reverse cholesterol transport. The hepatic remnant receptor, a distinct binding site on liver membranes that recognizes apo E but not apo B, appears to function in the clearance of chylomicrons (and probably VLDL) remnants from the circulation, but also is likely to be important in the recognition of apo E-containing HDL, and hence is likely to participate in the reverse cholesterol transport. Finally, there is now evidence for a third group of lipoprotein receptors that are present on the cell surface of macrophages. They appear to bind lipoproteins that have been altered chemically or biologically and probably serve a scavenger function. While many of the model systems for studying these macrophage receptors have focused on chemical modifications that are unlikely to occur in vivo, several lipoproteins that have been shown to interact with these receptors may be naturally occurring or result from biological processes. The discovery of the three receptor classes has resulted in a dramatic increase in the understanding of lipoprotein physiology and pathophysiology, and future studies should further expand our understanding of the regulation of lipoprotein metabolism and its relationship to hyperlipoproteinemia and atherosclerosis.