Compositional and metabolic heterogeneity of alpha 2- and beta-very-low-density lipoproteins in subjects with broad beta disease and endogenous hypertriglyceridemia.

The catabolism of alpha 2- and beta-very-low-density lipoproteins (VLDL) was studied in normolipidemic and hyperlipidemic subjects to determine whether differences in the catabolism of these subfractions are due to their composition. alpha 2-VLDL (cholesterol/triglyceride ratio, 00.18 +/- 0.06; and apoprotein E/C ratio, 0.27 +/- 0.22, n = 4) and beta-VLDL (cholesterol/triglyceride ratio, 0.67 +/- 0.13; and apoprotein E/C ratio, 1.05 +/- 0.52, n = 4) were isolated from subjects with broad beta disease, iodinated, and injected in five normolipidemic subjects, six with broad beta disease, and five with endogenous hypertriglyceridemia. VLDL, intermediate (IDL) and low-density lipoprotein (LDL) apoprotein (apo)-B radioactivity (tetramethylurea insoluble) following injection of 125I-labeled alpha 2- and beta-VLDL decayed biphasically in all subjects, and this decay in normolipidemic subjects was more rapid than in subjects with broad beta disease (P = 0.004) or endogenous hypertriglyceridemia (P = 0.004 for alpha 2- and P = 0.010 for beta-VLDL). The residence times, however, for the delipidation chain in alpha 2-VLDL were similar in all the subjects and varied from three to six hours. The decay of radioactivity in beta-VLDL in subjects with broad beta disease was much slower (residence time, 36.9 +/- 24.4 hr, n = 7) than in normolipidemic subjects (residence time, 7.56 +/- 4.6 hr, n = 5) or in subjects with endogenous hypertriglyceridemia (residence time, 10.6 +/- 4.65, n = 4). The residence time for alpha 2-VLDL was longer than for beta-VLDL in all subjects, suggesting that alpha 2-VLDL is a precursor to beta-VLDL. To test this directly, iodinated alpha 2-VLDL was injected into a subject with broad beta disease and the radioactivity in the subfractions was followed. The radioactivity from alpha 2-VLDL was transferred into beta-VLDL supporting, the notion that alpha 2-VLDL generated some beta-VLDL. Nicotinic acid treatment of a subject with broad beta disease accelerated the catabolism of alpha 2- and beta-VLDL without changing the VLDL composition.