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J. Lipid Res.
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A more recent version of this article appeared on October 1, 2003

Papers In Press, published online ahead of print July 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300209-JLR200
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Submitted on May 21, 2003
Revised on June 29, 2003
Accepted on July 7, 2003

Plasma turnover of HDL ApoC-I, ApoC-III and ApoE in humans.In Vivo evidence for a link between HDL ApoC-IIIand ApoA-I metabolism

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

Hyperlipidemia and Atherosclerosis Research Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7

Corresponding Author: cohnj{at}ircm.qc.ca

Numerous factors are known to affect the plasma metabolism of high-density lipoproteins (HDL). In order to better define the role of HDL apolipoproteins (apo) in determining plasma HDL concentrations, the aim of the present study was: a) to compare the in vivo rate of plasma turnover of HDL apos (i.e., 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 (HDL-C) levels ranging from 0.56-1.66 mmol/l and HDL apoA-I levels ranging from 89-149 mg/dl. Plasma kinetics of HDL apos were investigated using a primed constant (12h) infusion of deuterated leucine. Plasma HDL apo 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 (TR) 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-C 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 apoE, apoC-III and apoC-I levels were all positively related to their TRs and not their RTs. HDL apoC-III TR was postively correlated to HDL apoC-III (r = 0.73, P < 0.01), and with HDL-C and apoA-I (r = 0.54 and r = 0.53, P < 0.05, resp.). HDL apoC-III TR was in turn related to HDL apoA-I RT (r = 0.51, P < 0.05). 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.


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