title: Modulating effects of cholesterol feeding and simvastatin treatment on platelet-activating factor acetylhydrolase activity and lysophosphatidylcholine concentration.
abstract: 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.
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Fan
authors.forename: Eiso
authors.initials: E
authors.lastname: Shimoji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Uehara
authors.forename: Akira
authors.initials: A
authors.lastname: Matsunaga
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: 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
chemical_list: D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D019821:Simvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase