Abstract
The platelet-activating factor acetylhydrolase activity associated with high density lipoprotein (HDL-PAF-AH) may substantially contribute to the antioxidant, anti-inflammatory, and overall antiatherogenic effects of HDL. Two enzymes associated with HDL express PAF-AH catalytic activity, PAF-AH itself and paraoxonase-1 (PON1). The relative contribution of these enzymes in the expression of PAF-AH activity on HDL remains to be established. We investigated whether the PON1 polymorphisms (M55L and Q192R) or the PAF-AH polymorphism V379A could affect the PAF-AH activity associated with HDL in both normolipidemic and dyslipidemic (type IIA and IIB) populations. We show for the first time that the PON1 M55L polymorphism significantly affects the HDL-PAF-AH activity in all studied groups, the PON1 L55L individuals having lower enzyme activity compared to those having 1 M and 2 M alleles. No differences in the HDL content concerning the major apolipoprotein and lipid constituents were observed between individuals carrying the PON1 L55L and those with the M55M polymorphism. Our results provide evidence that PON1 significantly contributes to the pool of HDL-PAF-AH activity in human plasma, and suggest that the low PAF-AH activity in HDL carrying the PON1 L alloenzyme may be an important factor contributing to the low efficiency of this HDL in protecting LDL against lipid peroxidation.
Highlights
The platelet-activating factor acetylhydrolase activity associated with high density lipoprotein (HDL-PAFAH) may substantially contribute to the antioxidant, antiinflammatory, and overall antiatherogenic effects of HDL
Potential roles in the HDL antiinflammatory and antioxidant properties are played by two enzymes associated with this lipoprotein, platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON1) [2]
In the present study we investigated whether the PON1 polymorphisms (M55L and Q192R) or the PAF-AH polymorphism V379A could affect the PAF-AH activity in plasma and that associated with HDL in patients with dyslipidemia of type IIA or IIB, as well as in normolipidemic, apparently healthy volunteers
Summary
The platelet-activating factor acetylhydrolase activity associated with high density lipoprotein (HDL-PAFAH) may substantially contribute to the antioxidant, antiinflammatory, and overall antiatherogenic effects of HDL. Two enzymes associated with HDL express PAF-AH catalytic activity, PAF-AH itself and paraoxonase-1 (PON1). It is well established that HDL plays a protective role against atherogenesis and coronary heart disease (CHD) [1] This effect appears to be multifactorial and involves a number of mechanisms, including reverse cholesterol transport, as well as antiinflammatory and antioxidant activities. Potential roles in the HDL antiinflammatory and antioxidant properties are played by two enzymes associated with this lipoprotein, platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON1) [2]. Two of them are situated in exon 9 (V279F and Q281R) and have been described only in Japanese populations These mutations result in a complete loss of the enzyme activity and are associated with severe asthma, stroke, and cardiovascular disease [5, 6]. PON1 can hydrolyze oxidized phospholipids and cholesteryl ester hydroperoxides formed dur-
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