Last update:
07-Jul-2004

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.