J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M300198-JLR200 on December 1, 2003

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Journal of Lipid Research, Vol. 45, 448-455, March 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency

Bela F. Asztalos1,*, Katalin V. Horvath*, Kouji Kajinami*, Chorthip Nartsupha*, Caitlin E. Cox*, Marcelo Batista*, Ernst J. Schaefer*, Akihiro Inazu{dagger} and Hiroshi Mabuchi{dagger}

* Lipid Metabolism Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA
{dagger} Molecular Genetics of Cardiovascular Disorders, Division of Cardiovascular Medicine, Kanazawa University, Kanazawa, Japan

1 To whom correspondence should be addressed. e-mail: bela.asztalos{at}tufts.edu

Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had ~50% lower preß-1 and more than 2-fold higher levels of {alpha}-1 and pre{alpha}-1 particles than controls. Three of the five heterozygotes' {alpha}-1 particles also contained apoA-II, which was not seen in controls. Compound heterozygotes and homozygotes had very large particles not observed in controls and heterozygotes. These particles contained apoA-I, apoA-II, apoCs, and apoE. However, these subjects did not have decreased preß-1 levels.

Our data indicate that CETP deficiency results in the formation of very large HDL particles containing all of the major HDL apolipoproteins except for apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP-deficient patients, especially those with high levels of {alpha}-1 containing apoA-I but no apoA-II, represent an improved anti-atherogenic state, although this might not be the case for compound heterozygotes and homozygotes with very large, undifferentiated HDL particles.

Supplementary key words lipoproteins • high density lipoprotein subpopulations • reverse cholesterol transport


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