| Impact of atorvastatin treatment on platelet-activating factor acetylhydrolase and 15-F(2trans)-isoprostane in hypercholesterolaemic patients. | |
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MedLine Citation:
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PMID: 17214829 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: 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). CONCLUSION: 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. |
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Authors:
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Ghainsom D Kom; Edzard Schwedhelm; Renke Maas; Lydia Schneider; Ralf Benndorf; Rainer H Böger |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial Date: 2007-01-03 |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: 63 ISSN: 0306-5251 ISO Abbreviation: Br J Clin Pharmacol Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-05-18 Completed Date: 2007-09-27 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 672-9 Citation Subset: IM |
Affiliation:
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Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Centre Hamburg--Eppendorf, Hamburg, Germany. g.kom@uke.uni-hamburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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blood,
metabolism* Adult Anticholesteremic Agents / therapeutic use* Cholesterol, LDL / blood, metabolism* F2-Isoprostanes / blood, metabolism* Female Heptanoic Acids / therapeutic use* Humans Hypercholesterolemia / drug therapy* Male Middle Aged Pyrroles / therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/Anticholesteremic Agents; 0/Cholesterol, LDL; 0/F2-Isoprostanes; 0/Heptanoic Acids; 0/Pyrroles; 110862-48-1/atorvastatin; EC 3.1.1.47/1-Alkyl-2-acetylglycerophosphocholine Esterase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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