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

Abstract

Subfractions of radioiodinated d less than 1.019 g/ml lipoproteins were isolated by nonequilibrium density gradient ultracentrifugation (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. Subfractions containing a subspecies of very low density lipoproteins (VLDL) of particle diameter greater than 350 A were cleared rapidly from the plasma and formed only small amounts of low density lipoproteins (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 to 265 A, d = 1.030 to 1.040 g/ml). A similar LDL product was formed from subfractions containing intermediate density lipoproteins (IDL). Cholesterol-enriched subspecies within the smaller, denser portion of the IDL spectrum, however, yielded two additional products. One had size and density characteristic of the major human LDL-I subclass reported previously (265 to 275 A, d = 1.025 to 1.030 g/ml), while the other was yet larger (275 to 285 A) and overlapped normal IDL in size and density. In dysbetalipoproteinemic plasma, the metabolic precursors of the largest product were shifted from the IDL to the small VLDL (beta-VLDL) particle distribution. Since beta-VLDL are known to predispose to accelerated atherosclerosis in dysbetalipoproteinemia, it may be that metabolically homologous cholesterol-enriched IDL subspecies in other subjects have similar atherogenic properties.