Dissociable and nondissociable forms of platelet-activating factor acetylhydrolase in human plasma LDL: implications for LDL oxidative susceptibility

Platelet-activating factor acetylhydrolase (PAF-AH) is transported by lipop roteins in plasma and is thought to possess both anti-inflammatory and anti -oxidative activity. It has been reported that PAF-AH is recovered primaril y in small, dense LDL and HDL following ultracentrifugal separation of lipo proteins. In the present studies, we aimed to further define the distributi on of PAF-AH among lipoprotein fractions and subfractions, and to determine whether these distributions are affected by the lipoprotein isolation stra tegy (FPLC versus sequential ultracentrifugation) and LDL particle distribu tion profile. When lipoproteins were isolated by FPLC, the bull; (similar t o 85%) of plasma PAF-AH activity was recovered within LDL-containing fracti ons, whereas with ultracentrifugation, there was a redistribution to HDL (w hich contained similar to 18% of the activity) and the d > 1.21 g/ml fracti on (which contained similar to 32%). Notably, re-ultracentrifugation of iso lated LDL did not result in any further movement of PAF-AH to higher densit ies, suggesting the presence of dissociable and nondissociable forms of the enzyme on LDL. Differences were noted in the distribution of PAF-AH activi ty among LDL subfractions from subjects exhibiting the pattern A (primarily large, buoyant LDL) versus pattern B (primarily small, dense LDL) phenotyp e. In the latter group, there was a relative depletion of PAF-AH activity i n subfractions in the intermediate to dense range (d= 1.039-1.047 g/ml) wit h a corresponding increase in enzyme activity recovered within the d> 1.21 g/ml ultracentrifugal fraction. Thus, there appears to be a greater proport ion of the dissociable form of PAF-AH in pattern B subjects. In both popula tions, most of the nondissociable activity was recovered in a minor small, dense LDL subfraction. Based on conjugated dienes as a measure of lipid per oxidation, variations in PAF-AH activity appeared to contribute to variatio ns in oxidative behavior among ultracentrifugally isolated LDL subfractions . The physiologic relevance of PAF-AH dissociability and the minor PAF-AH-e nriched oxidation-resistant LDL subpopulation remains to be determined. Sci ence B.V. All rights reserved.