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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #179162
Title: APOLIPOPROTEIN COMPOSITION OF HDL IN CHOLESTERYL ESTER TRANSFER PROTEIN DEFICIENCY

Author
item ASZTALOS, BELA - TUFTS/HNRCA
item HORVATH, KATALIN - TUFTS/HNRCA
item KAJINAMI, KOUJI - TUFTS/HNRCA
item NARTSUPHA, CHORTHIP - TUFTS/HNRCA
item COX, CAITLIN - TUFTS/HNRCA
item BATISTA, MARCELO - TUFTS/HNRCA
item SCHAEFER, ERNST - TUFTS/HNRCA
item INAZU, AKIHIRO - KANAZAWA UNIV, JAPAN
item MABUCHI, HIROSHI - KANAZAWA UNIV, JAPAN

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2003
Publication Date: 3/1/2004
Citation: Asztalos, B.F., Horvath, K.V., Kajinami, K., Nartsupha, C., Cox, C.E., Batista, M., Schaefer, E.J., Inazu, A., Mabuchi, H. 2004. Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency. Journal of Lipid Research. 45(3):448-455.

Interpretive Summary: CETP plays a key role in HDL metabolism. It regulates total plasma HDL-cholesterol (HDL-C) level and also facilitates the remodeling of HDL particles. A high CETP concentration correlates with a low HDL-C level, a strong risk factor for coronary artery disease. On the other hand, Asian subjects with CETP deficiency have markedly increased HDL-C and apoA-I concentrations. In the present study, we investigated the size and apolipoprotein composition of HDL from the plasma of 9 homozygous, 4 compound heterozygous, and 5 heterozygous subjects with CETP deficiency and compared them with those of 50 age- and gender-matched controls.

Technical Abstract: 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 approximately 50% lower pre-beta-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 pre-beta-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.