title: HDL3-mediated inactivation of LDL-associated phospholipid hydroperoxides is determined by the redox status of apolipoprotein A-I and HDL particle surface lipid rigidity: relevance to inflammation and atherogenesis.
abstract: OBJECTIVE
  Small dense HDL3 particles of defined lipidome and proteome potently protect atherogenic LDL against free radical-induced oxidation; the molecular determinants of such antioxidative activity in these atheroprotective, antiinflammatory particles remain indeterminate.
  
  
  RESULTS
  Formation of redox-active phosphatidylcholine hydroperoxides (PCOOH) and redox-inactive phosphatidylcholine hydroxides (PCOH) was initiated in LDL by free radical-induced oxidation. Human HDL3 inactivated LDL-derived PCOOH (-62%, P<0.01) and enhanced accumulation of PCOH (2.1-fold, P<0.05); in parallel, HDL3 accumulated minor amounts of PCOOH. Enzyme-deficient reconstituted dense HDL potently inactivated PCOOH (-43%, P<0.01). HDL3-mediated reduction of PCOOH to PCOH occurred concomitantly with oxidation of methionine residues in HDL3-apolipoprotein AI (apoAI). Preoxidation of methionine residues by chloramine T markedly attenuated PCOOH inactivation (-35%); by contrast, inhibition of HDL3-associated enzymes was without effect. PCOOH transfer rates from oxidized LDL to phospholipid liposomes progressively decreased with increment in the rigidity of the phospholipid monolayer.
  
  
  CONCLUSIONS
  The redox status of apoAI and surface lipid rigidity represent major determinants of the potent HDL3-mediated protection of LDL against free radical-induced oxidation. Initial transfer of PCOOH to HDL3 is modulated by the surface rigidity of HDL3 particles with subsequent reduction of PCOOH to PCOH by methionine residues of apoAI.
authors.affiliation: Dyslipidemia and Atherosclerosis Research Unit (UMRS 939), National Institute for Health and Medical Research (INSERM), Hôpital de Pitié; UPMC Paris 6, University Paris Descartes, France.
authors.forename: Amal
authors.initials: A
authors.lastname: Zerrad-Saadi
authors.forename: Patrice
authors.initials: P
authors.lastname: Therond
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chantepie
authors.forename: Martine
authors.initials: M
authors.lastname: Couturier
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D053440:Lipoproteins, HDL3 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008715:Methionine / Q000737:chemistry; D008954:Models, Biological; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D005609:Free Radicals; D008054:Lipid Peroxides; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; D010743:Phospholipids; C099252:oxidized low density lipoprotein; D008715:Methionine