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.
Department of Advanced Medical Technology and Development, BML Inc, 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.
Takeshi
T
Kujiraoka
Hiroaki
H
Hattori
Mayumi
M
Ito
M Nazeem
MN
Nanjee
Mitsuaki
M
Ishihara
Makoto
M
Nagano
Tadao
T
Iwasaki
C Justin
CJ
Cooke
Waldemar L
WL
Olszewski
Irina P
IP
Stepanova
Tohru
T
Egashira
Norman E
NE
Miller
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