PLASMA KINETIC-BEHAVIOR IN HYPERLIPIDEMIC SUBJECTS OF A LIPIDIC MICROEMULSION THAT FINDS TO LOW-DENSITY-LIPOPROTEIN RECEPTORS

It was previously reported that a protein-free microemulsion (LDE) wit h structure roughly resembling that of the lipid portion of low densit y lipoprotein (LDL) was presumably taken up by LDL receptors when inje cted into the bloodstream. In contact with plasma, LDE acquires apolip oproteins (ape) including apo E that would be the ligand for receptor binding. Currently, apo were associated to LDE by incubation with high density lipoprotein (HDL). LDE-apo uptake by mononuclear cells showed a saturation kinetics, with an apparent K-m of 13.1 ng protein/mL. LD E-apo is able to displace LDL uptake by mononuclear cells with a K-i o f 11.5 ng protein/mL. LDE without apo is, however, unable to displace LDL. The uptake of C-14-HDL is not dislocated by increasing amounts of LDE-apo, indicating that HDL and LDE-apo do not bind to the same rece ptor sires. In human hyperlipidemias, LDE labeled with C-14-cholestery l ester behaved kinetically as expected for native LDL. LDE plasma dis appearance curve obtained from eight hypercholesterolemic patients was markedly slower than that from 10 control normolipidemic subjects [fr actional clearance rate (FCR) = 0.02 +/- 0.01 and 0.12 +/- 0.04 h(-1), respectively; P < 0.0001]. On the other hand, in four severely hypert riglyceridemic patients, LDE FCR was not significantly different from the controls (0.07 +/- 0.03 h(-1)). These results suggest that LDE can be a useful device to study lipoprotein metabolism.