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Journal of Lipid Research, Vol. 44, 1976-1983, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Plasma turnover of HDL apoC-I, apoC-III, and apoE in humans

Jeffrey S. Cohn^1,*, Rami Batal^*, Michel Tremblay^*, Hélène Jacques^*, Lyne Veilleux^*, Claudia Rodriguez^*, Orval Mamer and Jean Davignon^*

^* Hyperlipidemia and Atherosclerosis Research Group, Montréal, Québec, Canada
McGill University Biomedical Mass Spectrometry Unit, Montréal, Québec, Canada

¹ To whom correspondence should be addressed. e-mail: cohnj{at}ircm.qc.ca

Numerous factors are known to affect the plasma metabolism of HDL, including lipoprotein receptors, lipid transfer protein, lipolytic enzymes and HDL apolipoproteins. In order to better define the role of HDL apolipoproteins in determining plasma HDL concentrations, the aims of the present study were: a) to compare the in vivo rate of plasma turnover of HDL apolipoproteins [i.e., apolipoprotein A-I (apoA-I), apoC-I, apoC-III, and apoE], and b) to investigate to what extent these metabolic parameters are related to plasma HDL levels. We thus studied 16 individuals with HDL cholesterol levels ranging from 0.56–1.66 mmol/l and HDL apoA-I levels ranging from 89–149 mg/dl. Plasma kinetics of HDL apolipoproteins were investigated using a primed constant (12 h) infusion of deuterated leucine. Plasma HDL apolipoprotein levels were 41.8 ± 1.5, 9.7 ± 0.5, 4.9 ± 0.5, and 0.7 ± 0.1 µmol/l for apoA-I, apoC-I, apoC-III and apoE. Plasma transport rates (TRs) were 388.6 ± 24.7, 131.5 ± 12.5, 66.5 ± 9.1, and 31.4 ± 3.3 nmol·kg^-1·day^-1; and residence times (RTs) were 5.1 ± 0.4, 3.7 ± 0.3, 3.6 ± 0.3, and 1.1 ± 0.1 days, respectively. HDL cholesterol and apoA-I levels were significantly correlated with HDL apoA-I RT (r = 0.69 and r = 0.56), and were not significantly correlated with HDL apoA-I TR. In contrast, HDL apoC-I, apoC-III, and apoB levels were all positively related to their TRs and not their RTs. HDL apoC-III TR was postively correlated with levels of HDL apoC-III (r = 0.73, P < 0.01), and with those of HDL cholesterol and apoA-I (r = 0.54 and r = 0.53, P < 0.05, respectively). HDL apoC-III TR was in turn related to HDL apoA-I RT (r = 0.51, P < 0.05).

Together, these results provide in vivo evidence for a link between the metabolism of HDL apoC-III and apoA-I, and suggest a role for apoC-III in the regulation of plasma HDL levels.

Abbreviations: CHD, coronary heart disease; HL, hepatic lipase; SR-BI, scavenger receptor class B type I; TR, transport rate; TRL, triglyceride-rich lipoprotein

Supplementary key words apolipoprotein C-I • triglyceride • cholesterol • atherosclerosis • stable isotope • lipoprotein metabolism

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