Interactions of triglyceride-rich lipoproteins with receptors: modulation by thrombin.
Large VLDL from subjects with HTG but not normal humans bind with high affinity to both the classic LDL receptor present on all cells and the beta-VLDL receptor of macrophages. Binding of HTG-VLDL to the LDL receptor is mediated by a thrombin-accessible conformation of Apo E that is absent in normal VLDL. Binding of HTG VLDL to the beta-VLDL receptor appears to be mediated by one or more apo B species. We find that thrombin-accessible apo E is required for uptake of HTG-VLDL via the LDL receptor but not by the beta-VLDL receptor. Domains within apo B that are present in native chylomicrons and HTG-VLDL or created in vitro with thrombin appear to be required for binding to the beta-VLDL receptor but not the LDL receptor. Triglyceride-rich lipoproteins could be processed in vivo by thrombin or other proteases for preferential uptake and disposal by the beta-VLDL receptor pathway. This process may be involved in the foam cell accumulation and atherosclerosis associated with some types of hypertriglyceridemia.
D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; C036053:VLDL receptor; D013917:Thrombin