Characterization of subfractions of triglyceride-rich lipoproteins separated by gel chromatography from blood plasma of normolipemic and hyperlipemic humans

Abstract

As judged from measurements of the diameters of particles fixed with osmium tetroxide and shadowed with platinum, gel chromatography on 2% agarose has been shown to be an effective quantitative method for separating triglyceride-rich lipoproteins according to particle size. Particles in the size range of chylomicrons, uncontaminated by lipoproteins smaller than about 700 A or by other serum proteins, emerged in the void volume of the column, and very low density lipoproteins with diameters between 400 and 700 A were separated into fractions with average standard deviation of 71 A from the mean. Systematic comparison of the relationship between diameter and chemical composition of fractions obtained from subjects with various hyperlipoproteinemic disorders demonstrated a precise correlation consistent with a spherical model for these lipoproteins in which phospholipids, free cholesterol, and protein occupy a surface monolayer with an invariant thickness of 21.5 A surrounding a liquid core of triglycerides and cholesteryl esters. The chemical composition of very low density lipoproteins of given particle size in most recognized types of hyperlipemia was similar to that of normolipemic subjects, but particles in the size range of chylomicrons sometimes had higher contents of cholesteryl esters and free cholesterol. Results obtained in subjects with dysbetalipoproteinemia were consistent with the presence of three populations of particles. Two of these, with mean diameters of about 850 and 350 A, had unusually high cholesteryl ester content and reduced triglyceride content and may represent "remnants" of the metabolism of structurally normal chylomicrons and very low density lipoproteins, respectively. The third, a heterogeneous group with intermediate range of particle size and pre-beta mobility, may represent a population of very low density lipoproteins with relatively normal composition.