Metabolism of human intermediate and very low density lipoprotein subfractions from normal and dysbetalipoproteinemic plasma. In vivo studies in rat.

Abstract

Subtractions of radlolodinated d < 1.019 g/ml llpoproteins were Isolated by nonequillbrlum density gradient ultracentrlfugatlon (DGU) from normal and dysbetalipoproteinemic human plasma and were Injected into rats. Size and density (d) of lipoprotein products formed over 8 hours were assessed by gradient gel electrophoresis and equilibrium DGU, respectively. Subtractions containing a subspecies of very low density lipoprotelns (VLDL) of particle diameter > 350 A were cleared rapidly from the plasma and formed only small amounts of low density lipoprotelns (LDL). Fractions containing VLDL subspecies of smaller diameter (300 to 350 A) were cleared much more slowly, and formed greater amounts of a discrete LDL product with the characteristics of human LDL-II (peak particle diameter 255 L ow density lipoproteins (LDL) are believed to originate from the sequential catabolism of very low density lipoprotein (VLDL) precursors. As VLDL trtglyceride is hydrolyzed by lipoprotein lipase, smaller, cholesterol-enriched intermediate density lipoproteins (IDL) are formed and are subsequently converted to LDL by mechanisms that are poorly understood. In normal humans, nearly all of the protein moiety of plasma LDL derives from VLDL through IDL intermediates, 1 " 3 although in patients with familial hypercholesterolemia 4 ' 5 and in some primate species 6 independent production of LDL has been reported. A portion of the apolipoprotein (apo) B contained in VLDL, moreover, is removed from the circulation before conversion to LDL. This is the fate of 10% to 60% of the VLDL apo B in normal human subjects and a still greater proportion of the VLDL apo B in hypertriglyceridemic subjects 2 * 3S>7 "

Metabolic origins and clinical significance of LDL heterogeneity

“…However, the metabolic determinants of these parallel pathways are not understood. Studies in our laboratory have focused on the role of IDL heterogeneity in metabolic pathways leading to discrete LDL subspecies (1,2,68). The results have indicated that the small VLDL-2/IDL-1 particle spectrum includes precursors of mid-sized LDL-II, while IDL-2, which overlaps the size and density distribution of large LDL (LDL-I), also includes metabolic precursors of these particles (Fig.…”

Detection of two species of low density lipoprotein particles in cholesteryl ester transfer protein deficiency.

“…This transfer process is probably accomplished in an early phase of LDL formation, such as the VLDL or IDL phase, so that we cannot confirm the presence of the pathway for the smaller LDL in normal controls. Krauss 19 and Musliner et al 20 have reported multiple precursor-product relations involving individual VLDL, IDL, and LDL subpopulations and have suggested the existence of dual pathways for the production of IDL and LDL subspecies. They demonstrated the existence of two sizes of subpopulations in both VLDL and DDL, but only one in LDL, of normal human plasma.…”

Analysis and quantitation of biotinylated apoB-containing lipoproteins with streptavidin-Cy3

“…Apolipoprotein B (apoB) containing lipoproteins comprise multiple subclasses differing in size, density, and chemical composition (1)(2)(3)(4)(5)(6)(7)(8). The size distribution of these subclasses is commonly analyzed by non-denaturing GGE using stains for protein (Coomassie Brilliant Blue) or lipids (Sudan black, Oil Red O).…”