Last update:

   07-Jul-2004
 

Arch Hellen Med, 21(1), January-February 2004, 26-36

ORIGINAL PAPER

The effect of fenofibrate on plasma and HDL levels of PAF-acetylhydrolase:
A new modulating action of the fibrates?

V. TSIMIHODIMOS,1 A. KAKAFIKA,1 A. TAMBAKI,2
H. BAIRAKTARI,3 A. TSELEPIS,2 M. ELISAF1

1Pathology Sector, Medical School
2Biochemistry Laboratory, Department of Chemistry
3Biochemistry Laboratory, Medical School, University of Ioannina, Ioannina, Greece

OBJECTIVE Human plasma platelet activating factor acetylhydrolase (PAF-AH) is an enzyme associated mainly with the apolipoprotein B-containing lipoproteins. A small proportion of circulating enzyme activity is also associated with high-density lipoprotein (HDL). Plasma paraoxonase 1 (PON-1) is an esterase exclusively associated with HDL.

METHOD The effect of micronized fenofibrate (200 mg per day for 3 months) on PAFAH and PON-1 activities in patients with dyslipidemia of types IIA (n=18), IIB (n=23) and IV (n=30) was studied.

RESULTS Fenofibrate significantly reduced plasma PAF-AH activity in all patient groups. In type IIA patients this was mainly due to a fall in enzyme activity associated with the dense LDL subspecies, whereas in types IIB and IV patients the reduction 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 induction in enzyme activity associated with the HDL3c subfraction. Fenofibrate therapy did not affect either total serum PON-1 action on paraoxon and phenylacetate or the enzyme activities associated with the HDL subfractions, in either patient group.

CONCLUSIONS The fenofibrate- induced elevation of HDL-associated PAF-AH activity in dyslipidemic patients of type IIB and type IV and the reduction in enzyme activity associated with atherogenic apoB-containing lipoproteins in these patient groups as well as in type IIA patients, may represent a new and important overall anti-atherogenic effect of this potent lipid-modulating agent

Key words: Dyslipidemia, Fenofibrate, PAF-acetylhydrolase, Paraoxonase.


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