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Journal of Lipid Research, Vol. 44, 927-934, May 2003
Copyright © 2003 by Lipid Research, Inc.
* Department of Internal Medicine, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
Laboratory of Biological Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
Medical School, and Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
** 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
1 To whom correspondence should be addressed. e-mail: atselep{at}cc.uoi.gr
Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated mainly with the apolipoprotein B (apoB)-containing lipoproteins and primarily with LDL. A small proportion of enzymatic activity is also associated with HDL. Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL. The effect of fenofibrate on PAF-AH and PON1 activities in patients with dyslipidemias of Types IIA, IIB, and IV were studied. Fenofibrate reduced plasma PAF-AH activity in all patient groups. In Type IIA patients, this reduction was mainly due to a fall in enzyme activity associated with the dense LDL subspecies, whereas in Type IIB and Type IV patients, it was due to the decrease in PAF-AH activity associated with both the VLDL+IDL and dense LDL subspecies. Drug therapy in Type IIB and Type IV patients significantly increased the HDL-associated PAF-AH activity due to the increase in enzyme activity associated with the HDL-3c subfraction. Fenofibrate did not affect serum PON1 activities toward paraoxon and phenylacetate in either patient group.
The fenofibrate-induced elevation of HDL-associated PAF-AH activity in dyslipidemic patients of Type IIB and Type IV, as well as the reduction in enzyme activity associated with atherogenic apoB-containing lipoproteins in all patient groups, may represent a new and important antiatherogenic effect of this potent lipid-modulating agent.
Supplementary key words hyperlipidemia • platelet-activating factor-acetylhydrolase • paraoxonase
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