Lipid transfer protein-mediated distribution of HDL-derived cholesteryl esters among plasma apo B-containing...

The substrate specificity of lipid transfer protein has been examined in whole plasma in vitro by following the redistribution of high density lipoprotein (HDL)-derived [3H]cholesteryl ester (CE) into apolipoprotein (apo) B-containing lipoproteins using density gradient ultracentrifugation. HDL-derived [3H]CEs were incubated with plasma or isolated lipoprotein classes (very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein [LDL] subpopulations from the HDL donor) with and without lipoprotein lipase for 0.5-6 hours at 37 degrees C. After incubation, lipoproteins were separated into 38 fractions after density gradient ultracentrifugation, and radioactivity, protein, and cholesterol were monitored across the profiles. These studies indicate that 1) lipid transfer protein activity varied among the individuals as well as within an individual; 2) the majority of the [3H]CE was associated with LDL; 3) in most individuals (71%), more HDL-derived [3H]CE distributed within the buoyant LDL density region; and 4) the distribution of HDL-derived [3H]CE was similar to the distribution of lipoprotein lipase-derived "remnant" particles within buoyant LDL. These in vitro studies support the hypothesis that HDL-derived [3H]CEs vary in their distribution among apo B-containing particles and that more HDL-derived [3H]CEs are transferred to lipoproteins within the buoyant LDL density range. Additional studies suggest that lipoprotein heterogeneity within this density range, such as the presence of remnant-like lipoproteins, may contribute to the selective distribution of HDL-derived [3H]CE into buoyant LDL.