Further resolution and comparison of the heterogeneity of plasma low-density lipoproteins in human hyperlipoproteinemias: type III hyperlipoproteinemia, hypertriglyceridemia and familial hypercholesterolemia.
The heterogeneity of the plasma low-density lipoproteins (LDL) in subjects with type III hyperlipoproteinemia (3 cases), with hypertriglyceridemia (4 cases) and with the heterozygous form of familial hypercholesterolemia (FH, 4 cases) has been evaluated using a new, high resolution equilibrium density gradient ultracentrifugation procedure. The mass distribution profile, physicochemical properties, particle heterogeneity and apoprotein B content of a series of 13 LDL subfractions was examined in the 3 hyperlipidemic groups and the data were compared with those reported earlier in normolipidemic subjects. In FH, LDL mass was distributed as a narrow peak of d approximately 1.031-1.034 g/ml, whereas the distribution in hypertriglyceridemia was markedly asymmetric with a single peak of elevated density (d approximately 1.037-1.043 g/ml); the distribution in type III subjects was distinguished by its bi- or trimodal nature and broad profile. The chemical composition of LDL gradient subfractions in FH and in hypertriglyceridemia markedly resembled that of the respective parent LDL of d = 1.019-1.063 g/ml, displaying elevated proportions of cholesteryl ester in FH and of protein in hypertriglyceridemia. LDL subfractions in type III disease were enriched in free cholesterol. The Stokes diameters of LDL particles in corresponding subfractions from the 3 hyperlipidemic states were similar; however, whereas a single particle species was characteristic of each LDL subfraction in both FH and in our normolipidemic group, 2 species were frequently present in each subfraction in both type III and type IV diseases; in addition, subfractions from type III subjects occasionally exhibited 3 size species. Apolipoprotein B-100 was the predominant protein component in LDL subfractions from all 3 hyperlipidemic groups. Plasma LDL consist then of multiple particle species which constitute a particularly complex spectrum in type III hyperlipoproteinemia and in hypertriglyceridemia. The origin(s) of such particle subspecies is indeterminate at present; moreover, they may differ in their intravascular metabolism, in their degradation in tissues and in their relative atherogenicities.