Hypertriglyceridemia: lipoprotein receptors and atherosclerosis.

We have shown first, that apoB mediates the binding of small VLDL Sf 20-60 and IDL, as well as LDL, to the LDL receptor. Second, apoE of an appropriate, accessible conformation is required for the binding of large VLDL to the LDL receptor; HTG-VLDL Sf greater than 60 but not normal VLDL Sf greater than 60 have this apoE population. Third, the same population of apoE that mediates binding of HTG-VLDL Sf greater than 60 to the LDL receptor modulates its binding to the beta-VLDL receptor, but it is not required for the latter interaction. Fourth, a domain of processed apoB or apoB-48 in association with a domain of the inaccessible apoE is required for binding to and uptake by the beta-VLDL receptor. Fifth, our observations suggest that the abnormal catabolism of VLDL that occurs in hypertriglyceridemia may be explained by the abnormal uptake of HTG-VLDL by either the LDL or the beta-VLDL receptor pathway. Finally, we suggest that plasma proteases may route apoB/E-containing lipoproteins to macrophages for disposal, and this results in foam cell formation.