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Journal of Lipid Research, Vol. 43, 256-263, February 2002
Copyright © 2002 by Lipid Research, Inc.

Altered distribution of platelet-activating factor- acetylhydrolase activity between LDL and HDL as a function of the severity of hypercholesterolemia

Vasilis Tsimihodimosa, Sonia-Athena P. Karabinad, Afroditi P. Tambakid, Eleni Bairaktaric, George Miltiadousa, John A. Goudevenosb, Marios A. Carioloue, M. John Chapmanf, Alexandros D. Tselepisd, and Moses Elisafa
a Departments of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
b Cardiology, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
c Laboratory of Biological Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
d Medical School, and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
e Molecular Genetics Unit B-DNA Identification Laboratory, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
f Institut National de la Santé et de la Recherché, Unité 551, Hôpital de la Pitié, 83 Bd de l'Hôpital, 75651 Paris Cedex 13, France

Correspondence to: Alexandros D. Tselepis, To whom correspondence should be addressed., atselep{at}cc.uoi.gr (E-mail)

Platelet-activating factor-acetylhydrolase (PAF-AH) is a lipoprotein-associated phospholipase A2 capable of hydrolyzing platelet-activating factor (PAF) and oxidatively modified phospholipids. We studied the plasma- and lipoprotein-associated PAF-AH activity in patients with primary hypercholesterolemia. Thirty-eight unrelated patients with heterozygous familial hypercholesterolemia (HeteroFH), five patients with homozygous FH (HomoFH), and 33 patients with primary non-FH hypercholesterolemia (NonFH) participated in the study. In all patient groups the plasma PAF-AH activity was significantly elevated compared with 33 normolipidemic controls, the HomoFH having the highest and the NonFH patients showing the lowest enzyme activity. Gradient ultracentrifugation studies showed that this increase is not only due to the elevation in the plasma LDL but also to the increase in the PAF-AH activity associated with each LDL subfraction, being more profound in the small-dense LDL-5. Unlike LDL, no difference in the HDL-associated PAF-AH activity was observed among all groups. Consequently, an altered distribution of enzyme activity among apolipoprotein B (apoB)- and apolipoprotein A-I (apoA-I)-containing lipoproteins is observed in hypercholesterolemic patients, resulting in a significant decrease in the ratio of the HDL-associated PAF-AH to the total plasma enzyme activity compared with controls. This reduction is proportional to the increase of the plasma LDL-cholesterol (LDL-C) levels and consequently to the severity of the hypercholesterolemia.

Thus, the ratio of HDL-associated PAF-AH-total plasma enzyme activity may be useful as a potential marker of atherogenicity in subjects with primary hypercholesterolemia. — Tsimihodimos, V., S-A. P. Karabina, A. P. Tambaki, E. Bairaktari, G. Miltiadous, J. A. Goudevenos, M. A. Cariolou, M. J. Chapman, A. D. Tselepis, and M. Elisaf. Altered distribution of platelet-activating factor-acetylhydrolase activity between LDL and HDL as a function of the severity of hypercholesterolemia. J. Lipid Res. 2002. 43: 256–263.

Supplementary key words: familial hypercholesterolemia, low density lipoprotein, lipoprotein subspecies, high density lipoprotein, PAF-acetylhydrolase, polygenic hypercholesterolemia


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