New model for kinetic studies of HDL metabolism in humans

Abstract

Background: The aim of the study was to develop a new model for kinetic studies of Apolipoprotein A-I of HDL (Apo A-I-HDL) labelled with stable isotope by using HDL subclasses isolated with fast protein liquid chromatography (FPLC). Materials and methods: Apo A-I-HDL kinetics were studied by infusing [5.5.5-2H3]-leucine for 14 h in six healthy subjects. Preβ1 and αHDL were separated by FPLC and total HDL by ultracentrifugation (HDL-UC). Results: The tracer-to-tracee ratios were higher in preβ1 HDL than in HDL-UC or αHDL. Leucine enrichments found in HDL-UC were higher compared with αHDL, suggesting that HDL-UC were composed of a mixture of Apo A-I-αHDL and Apo A-I- preβ1 HDL. Kinetic analysis of data obtained from FPLC was achieved using a multicompartmental model, including a conversion between preβ1 and αHDL compartments. The production rate of preβ1 HDL was 7.72 ± 2.86 mg kg-1 d -1 (mean ± SD). Preβ1 HDL were converted to αHDL at a rate of 96.24 ± 42.99 pool d-1, and the synthesis rate of preβ1 HDL from αHDL was 10-fold slower: 7.09 ± 4.51 pool d-1. Apo A-I-FCR of HDL-UC was estimated using a one-compartment model (0.165 ± 0.074 pool d-1), and was higher but not significantly compared with FCR of Apo A-I-αHDL (0.112 ± 0.026 pool d-1) calculated with the new model. Conclusions: This study reports for the first time a model involving enrichments of Apo A-I in preβ1 and αHDL which allowed the measure of Apo A-I cycling within HDL fraction and will aid better understanding of kinetics of HDL in humans.