Modulating effects of cholesterol feeding and simvastatin treatment on platelet-activating factor acetylhydrolase activity and lysophosphatidylcholine concentration.
BACKGROUND
Platelet-activating factor acetylhydrolyse (PAF-AH) is an enzyme that degrades PAF and bioactive oxidized lipids. However, it has been reported to be a risk factor for coronary heart disease. The present study examined the effects of cholesterol feeding and simvastatin treatment on plasma PAF-AH activity.


METHODS
Japanese White rabbits (n=22) were fed a diet containing 0.3% cholesterol and 3% corn oil for 1 month, and then divided into two groups that continued to receive this diet with (treated) or without (control) treatment with simvastatin (0.01%) for another 2 months.


RESULTS
Cholesterol feeding increased and simvastatin treatment decreased apolipoprotein (apo) B-containing lipoprotein subfractions as characterized by capillary isotachophoresis, serum levels of total cholesterol, phospholipids, LDL-C, apoE, plasma and LDL-associated PAF-AH (LDL-PAF-AH) activities, and plasma lyso-PC concentration. Cholesterol feeding also increased apoB levels but decreased the LDL-PAF-AH/LDL-C ratio and did not change the plasma PAF-AH/lyso-PC ratio. Simvastatin treatment did not affect apoB levels and only slightly increased the LDL-PAF-AH/LDL-C ratio. Secretion of PAF-AH activity from monocyte-derived macrophages was increased by cholesterol feeding but not affected by simvastatin treatment. These results indicate that PAF-AH activity is increased by cholesterol feeding due to increased secretion of PAF-AH activity from macrophages and that PAF-AH activity is decreased by simvastatin due to increased removal of lipid and enzyme contents of LDL particles.


CONCLUSIONS
Cholesterol elevation by cholesterol feeding and cholesterol-lowering by simvastatin modulate plasma PAF-AH activity by different mechanisms.
Zhang
Bo
B
Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma Jonan-ku, Fukuoka 814-0180, Japan.
Fan
Ping
P
Shimoji
Eiso
E
Itabe
Hiroyuki
H
Miura
Shin-ichiro
S
Uehara
Yoshinari
Y
Matsunaga
Akira
A
Saku
Keijiro
K
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D019075:Electrophoresis, Capillary; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood; D008244:Lysophosphatidylcholines / Q000097:blood*; D008297:Male; D011817:Rabbits; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D019821:Simvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase