Altered distribution of plasma PAF-AH between HDLs and other lipoproteins in hyperlipidemia and diabetes mellitus

Platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 associated with lipoproteins that hydrolyzes platelet-activating factor (PAF) and oxidized phospholipids. We have developed an ELISA for PAF-AH that is more sensitive than previous methods, and have quantified HDL-associated and non-HDL-associated PAF-AH in healthy, hyperlipidemic, and diabetic subjects. In healthy subjects, plasma total PAF-AH concentration was positively correlated with PAF-AH activity and with plasma total cholesterol, triacylglycerol, LDL cholesterol and apolipoprotein B (apoB) concentrations (all P < 0.01). HDL-associated PAF-AH concentration was correlated positively with plasma apoA-I and HDL cholesterol. Subjects with hyperlipidemia (n = 73) and diabetes mellitus (n = 87) had higher HDL-associated PAF-AH concentrations than did controls (P < 0.01). Non-HDL-associated PAF-AH concentration was lower in diabetic subjects than in controls (P < 0.01). Both hyperlipidemic and diabetic subjects had lower ratios of PAF-AH to apoB (P < 0.01) and higher ratios of PAF-AH to apoA-I (P < 0.01) than did 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. Platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 associated with lipoproteins that hydrolyzes platelet-activating factor (PAF) and oxidized phospholipids. We have developed an ELISA for PAF-AH that is more sensitive than previous methods, and have quantified HDL-associated and non-HDL-associated PAF-AH in healthy, hyperlipidemic, and diabetic subjects. In healthy subjects, plasma total PAF-AH concentration was positively correlated with PAF-AH activity and with plasma total cholesterol, triacylglycerol, LDL cholesterol and apolipoprotein B (apoB) concentrations (all P < 0.01). HDL-associated PAF-AH concentration was correlated positively with plasma apoA-I and HDL cholesterol. Subjects with hyperlipidemia (n = 73) and diabetes mellitus (n = 87) had higher HDL-associated PAF-AH concentrations than did controls (P < 0.01). Non-HDL-associated PAF-AH concentration was lower in diabetic subjects than in controls (P < 0.01). Both hyperlipidemic and diabetic subjects had lower ratios of PAF-AH to apoB (P < 0.01) and higher ratios of PAF-AH to apoA-I (P < 0.01) than did 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. Platelet-activating factor acetylhydrolase (PAF-AH; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase, E.C.3.1.1.47) is a Ca2+-independent phospholipase A2 that catalyzes the conversion of platelet-activating factor (PAF) to lyso-PAF by hydrolyzing the acetyl group at the sn-2 position of the glycerol backbone (1Stafforini D.M. Prescott S.M. McIntyre T.M. Human plasma platelet-activating factor acetylhydrolase. Purification and properties.J. Biol. Chem. 1987; 262: 4223-4230Google Scholar, 2Stafforini D.M. McIntyre T.M. Carter M.E. Prescott S.M. Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.J. Biol. Chem. 1987; 262: 4215-4222Google Scholar, 3Stafforini D.M. Satoh K. Atkinson D.L. Tjoelker L.W. Eberhardt C. Yoshida H. Imaizumi T. Takamatsu S. Zimmerman G.A. McIntyre T.M. Gray P.W. Prescott S.M. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.J. Clin. Invest. 1996; 97: 2784-2791Google Scholar, 4Stafforini D.M. Prescott S.M. Zimmerman G.A. McIntyre T.M. Mammalian platelet-activating factor acetylhydrolases.Biochim. Biophys. Acta. 1996; 1301: 161-173Google Scholar, 5Stafforini D.M. McIntyre T.M. Zimmerman G.A. Prescott S.M. Platelet-activating factor acetylhydrolases.J. Biol. Chem. 1997; 272: 17895-17898Google Scholar, 6Tjoelker L.W. Stafforini D.M. Platelet-activating factor acetylhydrolases in health and disease.Biochim. Biophys. Acta. 2000; 1488: 102-123Google Scholar). As PAF is a potent lipid mediator involved in inflammatory disease (7Snyder F. Platelet-activating factor and its analogs: metabolic pathways and related intracellular processes.Biochim. Biophys. Acta. 1995; 1254: 231-249Google Scholar), inactivation of the bioactive phospholipid by PAF-AH has an antiinflammatory effect (8Watson A.D. Navab M. Hama S.Y. Sevanian A. Prescott S.M. Stafforini D.M. McIntyre T.M. Du B.N. Fogelman A.M. Berliner J.A. Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein.J. Clin. Invest. 1995; 95: 774-782Google Scholar, 9Lee C. Sigari F. Segrado T. Horkko S. Hama S. Subbaiah P.V. Miwa M. Navab M. Witztum J.L. Reaven P.D. All ApoB-containing lipoproteins induce monocyte chemotaxis and adhesion when minimally modified. Modulation of lipoprotein bioactivity by platelet-activating factor acetylhydrolase.Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1437-1446Google Scholar). PAF-AH also hydrolyzes phospholipids containing oxidatively fragmented residues at the sn-2 position, suggesting that it might also have an antiatherogenic effect (10Steinbrecher U.P. Pritchard P.H. Hydrolysis of phosphatidylcholine during LDL oxidation is mediated by platelet-activating factor acetylhydrolase.J. Lipid Res. 1989; 30: 305-315Google Scholar, 11Stremler K.E. Stafforini D.M. Prescott S.M. Zimmerman G.A. McIntyre T.M. An oxidized derivative of phosphatidylcholine is a substrate for the platelet-activating factor acetylhydrolase from human plasma.J. Biol. Chem. 1989; 264: 5331-5334Google Scholar, 12Stremler K.E. Stafforini D.M. Prescott S.M. McIntyre T.M. Human plasma platelet-activating factor acetylhydrolase. Oxidatively fragmented phospholipids as substrates.J. Biol. Chem. 1991; 266: 11095-11103Google Scholar, 13Stafforini D.M. Zimmerman G.A. McIntyre T.M. Prescott S.M. The platelet-activating factor acetylhydrolase from human plasma prevents oxidative modification of low-density lipoprotein.Trans. Assoc. Am. Physicians. 1992; 105: 44-63Google Scholar). Plasma PAF-AH binds to lipoproteins with high affinity (2Stafforini D.M. McIntyre T.M. Carter M.E. Prescott S.M. Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.J. Biol. Chem. 1987; 262: 4215-4222Google Scholar). Normally, most of the enzyme activity in plasma is associated with LDLs and the rest with HDLs (2Stafforini D.M. McIntyre T.M. Carter M.E. Prescott S.M. Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.J. Biol. Chem. 1987; 262: 4215-4222Google Scholar). Although the physiologic role of the enzyme in lipoprotein metabolism is poorly understood, it is thought to protect LDLs from oxidative modification (8Watson A.D. Navab M. Hama S.Y. Sevanian A. Prescott S.M. Stafforini D.M. McIntyre T.M. Du B.N. Fogelman A.M. Berliner J.A. Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein.J. Clin. Invest. 1995; 95: 774-782Google Scholar, 13Stafforini D.M. Zimmerman G.A. McIntyre T.M. Prescott S.M. The platelet-activating factor acetylhydrolase from human plasma prevents oxidative modification of low-density lipoprotein.Trans. Assoc. Am. Physicians. 1992; 105: 44-63Google Scholar). However, the plasma PAF-AH activity associated with LDLs is progressively lost during oxidative modification of the particle (14Dentan C. Lesnik P. Chapman M.J. Ninio E. PAF-acether-degrading acetylhydrolase in plasma LDL is inactivated by copper- and cell-mediated oxidation.Arterioscler. Thromb. 1994; 14: 353-360Google Scholar). Furthermore, oxygen radicals rapidly and irreversibly inactivate PAF-AH, providing a potential mechanism by which they might enhance the proinflammatory effects of PAF and oxidized phospholipids (15Ambrosio G. Oriente A. Napoli C. Palumbo G. Chiariello P. Marone G. Condorelli M. Chiariello M. Triggiani M. Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor.J. Clin. Invest. 1994; 93: 2408-2416Google Scholar). Approximately 4% of Japanese subjects are deficient in plasma PAF-AH activity, owing to PAF-AH gene mutations, such as V279F (3Stafforini D.M. Satoh K. Atkinson D.L. Tjoelker L.W. Eberhardt C. Yoshida H. Imaizumi T. Takamatsu S. Zimmerman G.A. McIntyre T.M. Gray P.W. Prescott S.M. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.J. Clin. Invest. 1996; 97: 2784-2791Google Scholar, 16Miwa M. Miyake T. Yamanaka T. Sugatani J. Suzuki Y. Sakata S. Araki Y. Matsumoto M. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.J. Clin. Invest. 1988; 82: 1983-1991Google Scholar) and Q281R (17Yamada Y. Yokota M. Loss of activity of plasma platelet-activating factor acetylhydrolase due to a novel Gln281→Arg mutation.Biochem. Biophys. Res. Commun. 1997; 236: 772-775Google Scholar). The frequency of plasma PAF-AH deficiency in children with severe bronchial asthma was 3-fold greater than normal (12%), suggesting that PAF-AH may play an important role in inflammatory and allergic responses (18Stafforini D.M. Numao T. Tsodikov A. Vaitkus D. Fukuda T. Watanabe N. Fueki N. McIntyre T.M. Zimmerman G.A. Makino S. Prescott S.M. Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.J. Clin. Invest. 1999; 103: 989-997Google Scholar). Many studies have suggested that deficiency of plasma PAF-AH is associated with inflammatory disease. It has been shown that plasma PAF-AH activity is decreased in patients with asthma (16Miwa M. Miyake T. Yamanaka T. Sugatani J. Suzuki Y. Sakata S. Araki Y. Matsumoto M. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.J. Clin. Invest. 1988; 82: 1983-1991Google Scholar), systemic lupus erythematosus (19Tetta C. Bussolino F. Modena V. Montrucchio G. Segoloni G. Pescarmona G. Camussi G. Release of platelet-activating factor in systemic lupus erythematosus.Int. Arch. Allergy Appl. Immunol. 1990; 91: 244-256Google Scholar), and septic shock (20Graham R.M. Stephens C.J. Silvester W. Leong L.L. Sturm M.J. Taylor R.R. Plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis.Crit. Care Med. 1994; 22: 204-212Google Scholar). These observations suggest that individuals with plasma PAF-AH deficiency are at increased risk of severe responses to allergic inflammatory have that PAF-AH mutation to inflammatory and allergic (8Watson A.D. Navab M. Hama S.Y. Sevanian A. Prescott S.M. Stafforini D.M. McIntyre T.M. Du B.N. Fogelman A.M. Berliner J.A. Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein.J. Clin. Invest. 1995; 95: 774-782Google Scholar, D.M. PAF acetylhydrolase gene and asthma Scholar). an of a PAF-AH mutation with was in patients with N. T. H. T. N. T. Sugatani J. Miwa M. S. Association of a missense mutation in the plasma platelet-activating factor acetylhydrolase gene with risk of in Scholar) and in with Y. S. H. M. Yokota M. Association of a of the plasma platelet-activating factor acetylhydrolase gene with in Japanese patients with Scholar). We have PAF-AH from human and to a ELISA that is more sensitive than previous and on of apolipoprotein B lipoproteins from We the to plasma PAF-AH concentrations and the distribution of enzyme mass between HDLs and lipoproteins in healthy, hyperlipidemic, and diabetic subjects. was from was from and A from from healthy and had was at the from patients with hyperlipidemia and and from and was in the of the for of hyperlipidemic subjects a such as a Lipid are shown in of total cholesterol, triacylglycerol, LDL cholesterol, and apoB and of apoA-I in hyperlipidemic and diabetic subjects than in controls. HDL cholesterol was lower in than in of healthy, hyperlipidemic, and diabetic of subjects cholesterol < from healthy < from healthy < from healthy < from healthy cholesterol < from healthy < from healthy cholesterol < from healthy < from healthy < from healthy < from healthy < from healthy apolipoprotein are as P < from healthy P < from healthy controls. in a apolipoprotein are as Plasma PAF-AH activity was determined as C. H. K. and of a phospholipase involved in the oxidative modification of low-density Thromb. Vasc. Biol. 1996; Scholar). PAF-AH was with for at The was by of an of and at for at the was The was with an of The in the was in a PAF-AH activity was also in an a T. M. Y. T. A. M. K. for serum platelet-activating factor acetylhydrolase Acta. 2000; Scholar). a substrate the of more in plasma in the of Purification of plasma PAF-AH was as C. H. K. and of a phospholipase involved in the oxidative modification of low-density Thromb. Vasc. Biol. 1996; Scholar). LDL was at LDL was in and at was by The was to a with and the was with the of the was at the with and at the was with and at The containing PAF-AH activity by and the was a with and with a of to The containing PAF-AH activity and the was a with with the and with The of the PAF-AH was by and by Human plasma PAF-AH was by from of human was as the and as the The was the was in of containing and was with and with and containing and The was the and the with containing and The was a with containing and and with containing The was to an and with containing and was containing and by to the The PAF-AH from E. of with T. T. M. M. M. T. T. H. of human plasma phospholipid by Chem. 2000; Scholar) with plasma PAF-AH in and the was PAF-AH was by and as The of was by by was with as and as with an plasma PAF-AH as T. T. M. M. M. T. T. H. of human plasma phospholipid by Chem. 2000; Scholar, T. T. M. T. T. E. S. H. A for human serum Lipid Res. 2000; Scholar). with PAF-AH, and from the with A for of Scholar). The of by ELISA with PAF-AH and by at by and The was from to the at and at The of and by ELISA and plasma PAF-AH and was the and was and for and of in was a by at The with of containing for at the had been with of containing of the and plasma and for at the had been of was to and the was for at the had been of was and the was for at the had been of substrate containing and was to the was by of of The was at by a and from as and was to of plasma (n = in to the total PAF-AH concentration by the concentrations by the ELISA to of The and of of the ELISA and (n = with the ELISA was with of plasma and serum for did the PAF-AH concentration as determined by the ELISA The ELISA was to the when lipoproteins from plasma with and from a for of HDL cholesterol The was with The and of for the HDL-associated PAF-AH concentration the and (n = plasma from healthy subjects was to plasma a for the V279F the of HDL-associated PAF-AH concentration by the ELISA was = Non-HDL-associated PAF-AH was by The V279F and Q281R of PAF-AH by the as M. S. K. M. T. M. Y. T. T. H. N. T. M. N. Y. novel missense in the gene in Japanese by Lipid Res. Scholar). and for mutation with to have of and a on the of and The and are shown in was by the ratios of with to with The of was determined by with results by and of and for of the PAF-AH gene platelet-activating factor The of are in in a PAF-AH, platelet-activating factor The of are in of plasma total cholesterol, triacylglycerol, and HDL cholesterol concentrations in a HDL cholesterol was of lipoproteins with and LDL cholesterol concentration was to and of the concentration of low-density lipoprotein cholesterol in of the Chem. Scholar). was determined by the as a was by the of during the of the of Scholar), and as by and H. T. J. of from to and Scholar). was a The LDL = was from human plasma by as T. T. M. M. M. T. T. H. of human plasma phospholipid by Chem. 2000; Scholar). as was for group by P < was The plasma PAF-AH and from the of a of These more than of total of the with plasma PAF-AH, and for PAF-AH and and LDLs from human plasma to with a the mass of which and was to that for human plasma PAF-AH C. H. K. and of a phospholipase involved in the oxidative modification of low-density Thromb. Vasc. Biol. 1996; Scholar). and PAF-AH was in the to in that to owing to the lower of PAF-AH in the was of of plasma Both with PAF-AH a enzyme activity, suggesting that they may with from the site of the enzyme of PAF-AH was a ELISA was as A ELISA for plasma PAF-AH was for and for a to and plasma of the was from the of to and by the a which of the total in the determined by the The concentration of a with as was a for the of the in containing to of per the as a was in containing to the PAF-AH concentration the was to that with the The ELISA was to and for PAF-AH concentrations as low as potential by low high the PAF-AH concentrations in plasma to and the that an between and was The was in the to effects of between in lipid apolipoprotein We for and Plasma with containing and the for PAF-AH concentration did from with containing Plasma total PAF-AH concentration by the ELISA was correlated with total PAF-AH PAF-AH concentration and activity in the of plasma of lipoproteins also positively These are shown in for PAF-AH concentration in healthy and are in of PAF-AH mass was associated with The concentrations of total and non-HDL-associated PAF-AH higher in than in Plasma total PAF-AH concentration was positively correlated with plasma total cholesterol = LDL cholesterol and apoB concentrations (all P < 0.01). These with The of non-HDL-associated PAF-AH concentration with LDL cholesterol and apoB concentrations in HDL-associated PAF-AH was correlated positively with HDL cholesterol and apoA-I and with LDL cholesterol and apoB (all P < 0.01) Non-HDL-associated and HDL-associated PAF-AH concentrations correlated with = P < PAF-AH < from < from < from healthy < from healthy < from healthy < from healthy < from healthy < from healthy < from healthy controls. < from < from healthy < from healthy < from healthy < from healthy are as P < from healthy P < from healthy P < from in a of HDL-associated PAF-AH concentration with HDL cholesterol and apoA-I are as In and HDL-associated PAF-AH concentration was greater in subjects than in healthy was in non-HDL-associated PAF-AH was in of the that LDL cholesterol and apoB concentrations higher than in and was between the in HDL cholesterol The of PAF-AH concentration with total cholesterol LDL cholesterol P < and apoB in hyperlipidemic subjects than in HDL-associated PAF-AH concentration was correlated with HDL cholesterol apoA-I The of non-HDL-associated PAF-AH to apoB was lower in hyperlipidemic subjects than in that of HDL-associated PAF-AH to apoA-I was greater In to the in HDL-associated and non-HDL-associated PAF-AH concentrations positively associated = P < of PAF-AH mass to apolipoprotein mass in healthy hyperlipidemic subjects, and diabetic < from healthy controls of the at position < from healthy controls of the at position < from healthy controls of the at position < from healthy controls of the at position < from healthy controls of the at position < from healthy controls of the at position < from healthy controls of the at position < from healthy controls of the at position are as P < from healthy controls of the at position P < from healthy controls of the at position in a are as As in the hyperlipidemic subjects, in and HDL-associated PAF-AH concentration was and non-HDL-associated concentration was lower in diabetic subjects than in healthy controls. was the that HDL cholesterol and apoA-I lower and LDL cholesterol and apoB greater than in controls. as in the hyperlipidemic subjects, the of non-HDL-associated PAF-AH to apoB was and the of HDL-associated PAF-AH to apoA-I was greater than in the controls HDL-associated and non-HDL-associated PAF-AH concentrations positively correlated with = P < 0.01). A missense mutation of V279F in the PAF-AH in of activity, is in Japanese subjects (16Miwa M. Miyake T. Yamanaka T. Sugatani J. Suzuki Y. Sakata S. Araki Y. Matsumoto M. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.J. Clin. Invest. 1988; 82: 1983-1991Google Scholar, D.M. Numao T. Tsodikov A. Vaitkus D. Fukuda T. Watanabe N. Fueki N. McIntyre T.M. Zimmerman G.A. Makino S. Prescott S.M. Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.J. Clin. Invest. 1999; 103: 989-997Google Scholar). In the the frequency for was and in hyperlipidemic subjects, and diabetic subjects, We also a healthy and a diabetic for the Q281R These results with for the Japanese (16Miwa M. Miyake T. Yamanaka T. Sugatani J. Suzuki Y. Sakata S. Araki Y. Matsumoto M. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.J. Clin. Invest. 1988; 82: 1983-1991Google Scholar, D.M. Numao T. Tsodikov A. Vaitkus D. Fukuda T. Watanabe N. Fueki N. McIntyre T.M. Zimmerman G.A. Makino S. Prescott S.M. Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.J. Clin. Invest. 1999; 103: 989-997Google Scholar). of the clinical of subjects, for the V279F mutation had lower and HDL-associated PAF-AH concentrations than subjects with PAF-AH In for the V279F PAF-AH was concentration in to the V279F at < from the at position < from the at position < from healthy < from healthy < from healthy controls. < from the at position < from healthy < from healthy < from healthy < from healthy controls. < from the at position < from healthy < from healthy are as P < from healthy P < from the at position P < from healthy controls. in a are as We have developed a ELISA for plasma PAF-AH PAF-AH from human The of the was by Both and with a in human plasma of which is the as that for plasma PAF-AH C. H. K. and of a phospholipase involved in the oxidative modification of low-density Thromb. Vasc. Biol. 1996; Scholar). with human LDLs with LDLs with and plasma PAF-AH a the of PAF-AH in plasma Our ELISA to to of plasma PAF-AH with A between plasma PAF-AH concentration and its activity suggested that active enzyme in Plasma PAF-AH concentration has been by with a ELISA M.J. C.J. K.E. P. phospholipase platelet-activating factor a potential risk factor for 2000; Scholar, C.J. M.J. A.D. J. K.E. M. A. phospholipase A2 as an of disease. of J. Med. 2000; Scholar). Plasma PAF-AH concentrations in healthy subjects M.J. C.J. K.E. P. phospholipase platelet-activating factor a potential risk factor for 2000; Scholar) and subjects C.J. M.J. A.D. J. K.E. M. A. phospholipase A2 as an of disease. of J. Med. 2000; Scholar) to that have in healthy Japanese subjects M.J. C.J. K.E. P. phospholipase platelet-activating factor a potential risk factor for 2000; Scholar) that plasma PAF-AH concentration correlated positively with plasma total cholesterol, triacylglycerol, LDL cholesterol, and apoB and with HDL cholesterol in normal subjects. in with the of HDL cholesterol. It has been that plasma PAF-AH activity is higher in subjects with hyperlipidemia V. E. J.A. Chapman M.J. M. A.D. platelet-activating factor acetylhydrolase activity in of and Thromb. Vasc. Biol. 22: Scholar) and in subjects with disease M.J. C.J. K.E. P. phospholipase platelet-activating factor a potential risk factor for 2000; Scholar, C.J. M.J. A.D. J. K.E. M. A. phospholipase A2 as an of disease. of J. Med. 2000; Scholar) than in normal subjects. We also high concentrations of PAF-AH in hyperlipidemic subjects (P < However, diabetic subjects did have PAF-AH they had plasma total cholesterol of the Japanese a of to at of the PAF-AH in an of for at position for have of enzyme In the and for the V279F mutation and for the Q281R The frequency for the V279F mutation was to that in (16Miwa M. Miyake T. Yamanaka T. Sugatani J. Suzuki Y. Sakata S. Araki Y. Matsumoto M. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.J. Clin. Invest. 1988; 82: 1983-1991Google Scholar, D.M. Numao T. Tsodikov A. Vaitkus D. Fukuda T. Watanabe N. Fueki N. McIntyre T.M. Zimmerman G.A. Makino S. Prescott S.M. Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.J. Clin. Invest. 1999; 103: 989-997Google Scholar). PAF-AH was in plasma from by concentrations in in the controls. Stafforini (3Stafforini D.M. Satoh K. Atkinson D.L. Tjoelker L.W. Eberhardt C. Yoshida H. Imaizumi T. Takamatsu S. Zimmerman G.A. McIntyre T.M. Gray P.W. Prescott S.M. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.J. Clin. Invest. 1996; 97: 2784-2791Google Scholar) have shown that the V279F is by have also shown that a Q281R in E. has the activity of the (18Stafforini D.M. Numao T. Tsodikov A. Vaitkus D. Fukuda T. Watanabe N. Fueki N. McIntyre T.M. Zimmerman G.A. Makino S. Prescott S.M. Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.J. Clin. Invest. 1999; 103: 989-997Google Scholar). We subjects with the Q281R PAF-AH concentration was low = suggesting that the Q281R may subjects with PAF-AH, the concentration of PAF-AH was greater in hyperlipidemic subjects than in was the for the V279F Plasma HDL-associated PAF-AH of was positively correlated with HDL-associated PAF-AH The of PAF-AH activity in HDLs in healthy Japanese subjects was lower than in (2Stafforini D.M. McIntyre T.M. Carter M.E. Prescott S.M. Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.J. Biol. Chem. 1987; 262: 4215-4222Google Scholar), suggesting that the distribution of the enzyme between HDLs and LDLs may by Our that in normal subjects, the mass of non-HDL-associated PAF-AH was correlated positively with LDL cholesterol and apoB that of HDL-associated PAF-AH was correlated positively with HDL cholesterol and apoA-I that the distribution of the enzyme lipoproteins is determined in by Our in hyperlipidemic and diabetic subjects that the distribution of PAF-AH between HDLs and LDLs is also by In of subjects, HDL-associated PAF-AH concentration was greater than in owing to a greater mass of enzyme per of the HDL in the of non-HDL-associated PAF-AH to apoB was lower than in the a lower mass of enzyme per LDL particle, of which of These in the mass of enzyme per HDL LDL particle the normal of concentration to the HDL and LDL concentrations in Our are with of V. E. G. J.A. Chapman M.J. A.D. M. distribution of platelet-activating factor-acetylhydrolase activity between LDL and HDL as a of the severity of Lipid Res. Scholar), that plasma total PAF-AH activity was greater in subjects with than in normal subjects, and for apoB It is also of that PAF-AH activity was by a in T.M. G. Berliner J.A. R.M. of and platelet-activating factor acetylhydrolase in Lipid Res. Scholar), and was to high in human apoA-I D. M. M. D. P. Ninio E. Effect of of human in and on platelet-activating factor acetylhydrolase and Thromb. Vasc. Biol. 2000; Scholar). of hyperlipidemia with increased HDL-associated PAF-AH activity V. A. E. Chapman M.J. M. A.D. HDL-associated enzyme activity associated with Lipid Res. Scholar). These results with that the distribution of PAF-AH between LDLs and HDLs is determined by the concentrations of the also by that the of the enzyme to the The of to N. E. was of platelet-activating factor acetylhydrolase