Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on paraoxonase and platelet-activating factor acetylhydrolase in human plasma and tissue fluid.
We have previously shown that intravenous apolipoprotein (apo) A-I/phosphatidylcholine (apo A-I/PC) discs increase plasma high-density lipoprotein (HDL) concentration in humans. We have now studied the associated changes in two enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH) that are carried in whole or in part by HDLs, and are thought to influence atherogenesis by hydrolyzing oxidized phospholipids in lipoproteins. Apo A-I/PC discs (40 mg/kg over 4 h) were infused into eight healthy males. Although plasma apo A-I and HDL cholesterol increased on average by 178 and 158%, respectively, plasma total PON and total PAF-AH concentrations did not rise. By the end of the infusion, HDL-associated PAF-AH had increased by 0.56 +/- 0.14 microg/mL (mean +/- S.D., P < 0.01), and nonHDL-associated PAF-AH had decreased by 0.84 +/- 0.11 microg/mL (P < 0.05). These changes were accompanied by an increase in the HDL-associated PAF-AH/apo A-I ratio from 0.19 to 0.35 (P < 0.05), and by a decrease in the nonHDL-associated PAF-AH/apo B ratio from 2.1 to 1.4 (P < 0.05). No changes in PON or PAF-AH concentrations were detected in prenodal lymph (tissue fluid), collected continuously from the leg. Our results show that the total concentrations of PON and PAF-AH in plasma are uninfluenced by plasma HDL concentration. PAF-AH transfers readily between HDLs and LDLs in vivo, and its distribution between them is determined partly by their relative concentrations and partly by HDL composition.
Kujiraoka
Takeshi
T
Department of Advanced Medical Technology and Development, BML Inc, 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.
Hattori
Hiroaki
H
Ito
Mayumi
M
Nanjee
M Nazeem
MN
Ishihara
Mitsuaki
M
Nagano
Makoto
M
Iwasaki
Tadao
T
Cooke
C Justin
CJ
Olszewski
Waldemar L
WL
Stepanova
Irina P
IP
Egashira
Tohru
T
Miller
Norman E
NE
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000328:Adult; D016632:Apolipoprotein A-I / Q000008:administration & dosage* / Q000097:blood; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D043303:Aryldialkylphosphatase / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008196:Lymph / Q000201:enzymology; D008297:Male; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000097:blood
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D010713:Phosphatidylcholines; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase