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Papers In Press, published online ahead of print July 16, 2003
J. Lipid Res., doi:10.1194/jlr.D300021-JLR200
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Advanced Medical Technology and Development, BML, Inc., Kawagoe, Saitama 350-1101
Corresponding Author: hhiro{at}bml.co.jp
Platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 that hydrolyzes platelet-activating factor (PAF) and oxidized phospholipids, and is assoiciated with lipoproteins. We have developed an ELISA for PAF-AH, which is more sensitive than previous methods, and have used it to quantify high density lipoprotein (HDL)-associated and nonHDL-associated PAF-AH in healthy, hyperlipidemic and diabetic subjects. In healthy subjects plasma total PAF-AH concentration was greater in men than in women, (1.38 ± 0.57 [n=69] vs 1.09 ± 0.45 µg/mL [n=29], mean ± SD, P<0.01), and was positively correlated with PAF-AH activity and with plasma total cholesterol, triacylglycerol, low density lipoprotein (LDL) cholesterol and apo B concentrations (all P < 0.01). HDL-associated PAF-AH concentration was correlated n positively with plasma apo A-I and HDL cholesterol. Heterozgotes for the common mutation at position 279 (V279F) had lower total PAF-AH concentrations (0.79 ± 0.24 µg/mL, n=37) than subjects with the wild type (1.61 ± 0.44 µg/mL, P<0.01); PAF-AH was not detectable in two homozygotes. Subjects with hyperlipidemia (n=69) had higher HDL-associated PAF-AH concentrations than controls (0.61 ± 0.32 vs 0.14 ± 0.07 µg/mL, P < 0.01). Subjects with diabetes mellitus (n = 87) had higher concentrations of HDL-associated PAF-AH (0.50 ± 0.23 µg/mL , P<0.01) and lower concentrations of nonHDL-associated PAF-AH (0.86 ±0.46 vs 1.15 ± 0.51 µg/mL (P<0.01) than controls. Both hyperlipidemic and diabetic subjects had lower ratios of PAF-AH to apo B (P < 0.01) and higher ratios of PAF-AH to apo A-I (P<0.01) than controls. Our results show that the distribution of PAF-AH mass between HDLs and LDLs is determined partly by the concentrations of the lipoproteins and partly by the mass of enzyme per lipoprotein particle, which is disturbed in hyperlipidemia and diabetes mellitus.
Revised on July 14, 2003
Accepted on July 14, 2003
Associations of platelet-activating factor acetylhydrolase with plasma lipoproteins in humans: Altered distributions between HDLs and other lipoproteins in hyperlipidemia and diabetes mellitus
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