title: High density lipoprotein efficiently accepts surface but not internal oxidised lipids from oxidised low density lipoprotein.
abstract: OBJECTIVE
  Oxidised low density lipoprotein (oxLDL) contributes to atherosclerosis, whereas high density lipoprotein (HDL) is known to be atheroprotective due, at least in part, to its ability to remove oxidised lipids from oxLDL. The molecular details of the lipid transfer process are not fully understood. We aimed to identify major oxidised lipid species of oxLDL and investigate their transfer upon co-incubation with HDL with varying levels of oxidation.
  
  
  RESULTS
  A total of 14 major species of oxidised phosphatidylcholine and oxidised cholesteryl ester from oxLDL were identified using an untargeted mass spectrometry approach. HDL obtained from pooled plasma of normolipidemic subjects (N=5) was oxidised under mild and heavy oxidative conditions. Non-oxidised (native) HDL and oxidised HDL were co-incubated with oxLDL, re-isolated and lipidomic analysis was performed. Lipoprotein surface lipids, oxidised phosphatidylcholines and oxidised cholesterols (7-ketocholesterol and 7β-hydroxycholesterol), but not internal oxidised cholesteryl esters, were effectively transferred to native HDL. Saturated and monounsaturated lyso-phosphatidylcholines were also transferred from the oxLDL to native HDL. These processes were attenuated when HDL was oxidised under mild and heavy oxidative conditions. The impaired capacities were accompanied by an increase in a ratio of sphingomyelin to phosphatidylcholine and a reduction in phosphatidylserine content in oxidised HDL, both of which are potentially important regulators of the oxidised lipid transfer capacity of HDL.
  
  
  CONCLUSIONS
  Our study has revealed the differential transfer efficiency of surface and internal oxidised lipids from oxLDL and their acceptance onto HDL. These capacities were modulated when HDL was itself oxidised.
authors.affiliation: Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Victoria, Australia.
authors.forename: Aliki A
authors.initials: AA
authors.lastname: Rasmiena
authors.affiliation: Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Barlow
authors.affiliation: Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Metabolic Research Centre, School of Medicine and Pharmacology, The University of Western Australia, Western Australia, Australia.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Ng
authors.affiliation: Metabolomics Australia, Bio21 Institute, Parkville, Victoria, Australia.
authors.forename: Dedreia
authors.initials: D
authors.lastname: Tull
authors.affiliation: Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Victoria, Australia. Electronic address: peter.meikle@bakeridi.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
mesh_terms: D000328:Adult; D000368:Aged; D001692:Biological Transport; D002788:Cholesterol Esters / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D005215:Fasting; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000737:chemistry; D007653:Ketocholesterols / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000302:isolation & purification; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000302:isolation & purification; D008244:Lysophosphatidylcholines / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D002788:Cholesterol Esters; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D016877:Oxidants; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D013109:Sphingomyelins; D014280:Triglycerides; C099252:oxidized low density lipoprotein; C011724:cholest-5-en-3 beta,7 alpha-diol; D003300:Copper; C003001:7-ketocholesterol; C029892:cupric chloride
keywords: Anti-oxidative; Cholesteryl ester; Lipidomic; Oxysterols; Phosphatidylcholine; Transfer