New model for kinetic studies of HDL metabolism in humans.
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).


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Chétiveaux
M
M
CHU Hôtel Dieu, Nantes, France.
Ouguerram
K
K
Zair
Y
Y
Maugère
P
P
Falconi
I
I
Nazih
H
H
Krempf
M
M
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D007554:Isotopes / Q000493:pharmacokinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000493:pharmacokinetics*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008954:Models, Biological
D016632:Apolipoprotein A-I; D053442:High-Density Lipoproteins, Pre-beta; D007554:Isotopes; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL