title: Proteomic and lipidomic analyses of paraoxonase defined high density lipoprotein particles: Association of paraoxonase with the anti-coagulant, protein S.
abstract: OBJECTIVE
  Characterizing high density lipoprotein (HDL) particles and their relevance to HDL function is a major research objective. One aim is to identify functionally distinct particles. To try to limit both functional and compositional heterogeneity the present study focused on paraoxonase-1 (PON1) as a target for isolation of a minor HDL subfraction.
  
  
  METHODS
  Immunoaffinity techniques were applied to isolate PON1-containing HDL (P-HDL) and total HDL (T-HDL), which were subsequently characterized and compared.
  
  
  RESULTS
  Analyses of the lipidomes showed significant differences between the fractions in the relative concentrations of individual lipid subspecies, notably reduced levels of unsaturated lysophosphatidylcholine (p < 0.05) in P-HDL (reflected in a significantly reduced total lysophosphatidylcholine polyunsaturated fatty acid content, p < 0.004). Significant differences were also observed for the proteomes. P-HDL was highly enriched in the anti-coagulant, vitamin K activated protein S (prot S) (p < 0.0001), and alpha2 macroglobulin (p < 0.01), compared to T-HDL. Conversely, procoagulant proteins kininogen 1 and histidine-rich glycoprotein were largely excluded from P-HDL. Immunoabsorption of PON1 from plasma significantly reduced prot S anti-coagulant activity.
  
  
  CONCLUSIONS
  The P-HDL lipidome and proteome showed significant differences from T-HDL. Enrichment in anti-coagulation proteins indicates complementary functionalities within P-HDL particles and underlines their anti-atherosclerotic potential.
authors.affiliation: Clinical Diabetes Unit, Department of Medical Specialities, Medical Faculty, University of Geneva, Geneva, Switzerland.
authors.forename: Xenia
authors.initials: X
authors.lastname: Moren
authors.affiliation: INSERM, UMR-ICAN, 1166, University of Pierre and Marie Curie - Paris 6, Pitié - Salpétrière University Hospital, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lhomme
authors.affiliation: Department of Genetic and Laboratory Medicine, University Hospital, Geneva, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bulla
authors.affiliation: Translational Biomarker Group (TBG), Department of Human Protein Sciences, University Medical Centre, University of Geneva, Geneva, Switzerland.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
authors.affiliation: INSERM, UMR-ICAN, 1166, University of Pierre and Marie Curie - Paris 6, Pitié - Salpétrière University Hospital, Paris, France.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
authors.affiliation: Clinical Diabetes Unit, Department of Medical Specialities, Medical Faculty, University of Geneva, Geneva, Switzerland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
mesh_terms: D000925:Anticoagulants / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D006801:Humans; D007163:Immunosorbent Techniques; D008075:Lipoproteins, HDL / Q000032:analysis* / Q000378:metabolism; D010316:Particle Size; D017293:Protein S / Q000378:metabolism*; D040901:Proteomics
chemical_list: D000925:Anticoagulants; D008075:Lipoproteins, HDL; D017293:Protein S; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Apolipoprotein; Atherosclerosis; Coagulation; HDL; Lipidomics