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.
D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; D013917:Thrombin