Relationships between LDL density and kinetic heterogeneity in subjects with normolipidemia and familial combined hyperlipidemia using density gradient ultracentrifugation.

Abstract

The metabolism of heterogeneous subpopulations of low density lipoprotein (LDL) apoB100 was examined in three normolipidemic and two familial combined hyperlipidemic subjects. Autologous radioiodinated plasma LDL (1.019 less than d less than 1.063 g/ml) were injected into each subject and the disappearance and appearance of radiolabeled lipoproteins into various LDL subpopulations were examined using density gradient ultracentrifugation. Eleven to 13 fractions (-320 microliter each) were collected within LDL defined uniquely in each subject. In all subjects, the disappearance of radiolabeled LDL from plasma was biexponential. However, changes with time in the distribution of radiolabeled LDL among the various LDL density subpopulations revealed complex metabolic behavior that differed among the subjects. When the relationships between density and kinetic characteristics were examined in more detail by following the disappearance of individual fractions defining LDL in each subject, the data suggested that: 1) the kinetic behavior of the LDL fractions was more complex than suggested by the disappearance of radiolabeled LDL from plasma: 2) certain fractions within specific density ranges were kinetically similar; 3) distinct differences in the disappearance curves among the fractions occurred within narrow density ranges; and 4) precursor-product relationships were seen among specific LDL density fractions and varied from subject to subject. These studies underscore the complexities of plasma LDL apoB-100 metabolism. More detailed characterizations of the kinetic behavior of various LDL subpopulations should help in our understanding of the origin(s) and potential physiological consequences of different LDL subpopulations.