title: HDL is the major lipoprotein carrier of plasma F2-isoprostanes.
abstract: Enhanced oxidative stress is implicated in the development of atherosclerosis in humans and animal models. F(2)-isoprostanes are formed in vivo via free radical peroxidation of arachidonic acid, and their quantification has allowed assessment of oxidative stress in vivo. F(2)-isoprostanes associate with lipids, although their distribution in human plasma lipoproteins is unknown. Our aim was to determine the distribution and levels of F(2)-isoprostanes in lipoproteins isolated from human plasma by ultracentrifugation and fast protein liquid chromatography (FPLC). F(2)-isoprostanes were significantly higher in HDL compared with LDL or VLDL after isolation by ultracentrifugation or FPLC. Furthermore, HDL3 particles contained elevated levels of F(2)-isoprostanes compared with HDL2. Platelet activating factor acetylhydrolase (PAF-AH), which hydrolyses esterified F(2)-isoprostanes from phospholipids, was predominantly associated with LDL. Reduced F(2)-isoprostanes in LDL may be related to higher PAF-AH activity in LDL. Paraoxonase 1 (PON-1) activity was associated with HDL2 and may be a contributing factor to the lower F(2)-isoprostanes in HDL2 compared with HDL3. Further studies are required to establish the implications of these findings on HDL function.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, Perth WA 6847, Australia.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Proudfoot
authors.forename: Anne E
authors.initials: AE
authors.lastname: Barden
authors.forename: Wai Mun
authors.initials: WM
authors.lastname: Loke
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.forename: Ian B
authors.initials: IB
authors.lastname: Puddey
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000578:Amidines / Q000494:pharmacology; D016718:Arachidonic Acid / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000097:blood; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D016877:Oxidants / Q000494:pharmacology
chemical_list: D000578:Amidines; D002352:Carrier Proteins; D028441:F2-Isoprostanes; D008054:Lipid Peroxides; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D016877:Oxidants; D016718:Arachidonic Acid; C046728:2,2'-azobis(2-amidinopropane); D019787:Linoleic Acid; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human