New model for kinetic studies of HDL metabolism in humans.

Abstract

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). Apo A-I-HDL kinetics were studied by infusing [5.5.5-(2)H(3)]-leucine for 14 h in six healthy subjects. Prebeta(1) and alphaHDL were separated by FPLC and total HDL by ultracentrifugation (HDL-UC). The tracer-to-tracee ratios were higher in prebeta(1) HDL than in HDL-UC or alphaHDL. Leucine enrichments found in HDL-UC were higher compared with alphaHDL, suggesting that HDL-UC were composed of a mixture of Apo A-I-alphaHDL and Apo A-I-prebeta(1) HDL. Kinetic analysis of data obtained from FPLC was achieved using a multicompartmental model, including a conversion between prebeta(1) and alphaHDL compartments. The production rate of prebeta(1) HDL was 7.72 +/- 2.86 mg kg(-1) d(-1) (mean +/- SD). Prebeta(1) HDL were converted to alphaHDL at a rate of 96.24 +/- 42.99 pool d(-1), and the synthesis rate of prebeta(1) HDL from alphaHDL 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-alphaHDL (0.112 +/- 0.026 pool d(-1)) calculated with the new model. This study reports for the first time a model involving enrichments of Apo A-I in prebeta(1) and alphaHDL which allowed the measure of Apo A-I cycling within HDL fraction and will aid better understanding of kinetics of HDL in humans.