title: Impact of atorvastatin treatment on platelet-activating factor acetylhydrolase and 15-F(2trans)-isoprostane in hypercholesterolaemic patients.
abstract: OBJECTIVE
  Isoprostanes are the product of free radical oxidation of arachidonic acid, whose hydrolysis from phospholipids is presumably catalysed by phospholipases A(2) (PLA(2)s) such as group IIA or V PLA(2)s, or group VII PLA(2)[platelet-activating factor acetylhydrolase (PAF-AH), lipoprotein-associated phospholipase]. Atorvastatin reduces concentrations of low-density lipoprotein (LDL), with which PAF-AH is associated, and PLA(2)s' protein concentrations. We investigated the effect of atorvastatin on PLA(2)s and PAF-AH activity and the urinary excretion of 15-F(2trans)-isoprostane (15-F(2t)-IsoP, 8-iso-PGF(2alpha), iPF(2alpha)-III).
  
  
  METHODS
  Twenty-four hypercholesterolaemic individuals naive to lipid-lowering therapy were randomized to atorvastatin 40 mg or placebo for 6 weeks. The 15-F(2t)-isoP urinary excretion (gas chromatography/mass spectrometry), PAF-AH and group IIA and V PLA(2) activities (photometry) were assessed at baseline and end-point.
  
  
  RESULTS
  At end-point, 15-F(2t)-isoP urinary excretion concentrations as well as PLA(2)s' activity were unchanged under atorvastatin (mean change 0.21 +/- 1.79 ng h(-1), 95% confidence interval -0.92, 1.35 and 0.33 +/- 0.94 nmol min(-1) ml(-1), -0.27, 0.93) and under placebo (mean change 0.69 +/- 1.69 ng h(-1), -0.52, 1.90 and 1.29 +/- 2.16 nmol min(-1) ml(-1), -0.25, 2.84). Atorvastatin treatment decreased total (P < 0.001) and LDL-cholesterol (P < 0.001) but had no effect on high-density lipoprotein. PAF-AH activity was lowered in the atorvastatin group (mean change - 5.27+/- 1.96 nmol min(-1) ml(-1), -6.51, -4.03, P < 0.001) but not in the placebo group (mean change 1.02 +/- 1.64 nmol min(-1) ml(-1), 0.15, 2.20), and the change in PAF-AH activity was correlated with that in total (P = 0.03) and LDL-cholesterol (P = 0.03).
  
  
  CONCLUSIONS
  Our results show a lowering effect of atorvastatin on PAF-AH activity associated with its lipid-lowering effect and exclude a key role of PAF-AH in the liberation of 15-F(2t)-isoP from phospholipids.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Centre Hamburg--Eppendorf, Hamburg, Germany. g.kom@uke.uni-hamburg.de
authors.forename: Ghainsom D
authors.initials: GD
authors.lastname: Kom
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Lydia
authors.initials: L
authors.lastname: Schneider
authors.forename: Ralf
authors.initials: R
authors.lastname: Benndorf
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000097:blood / Q000378:metabolism*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D028441:F2-Isoprostanes; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase