title: Nonenzymatic glycation impairs the antiinflammatory properties of apolipoprotein A-I.
abstract: OBJECTIVE
  The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I.
  
  
  RESULTS
  Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I(N)), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I(Glyc in vitro)), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I(Glyc in vivo)), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I(N), (A-I(N))rHDL, or apoA-I(Glyc in vitro), (A-I(Glyc in vitro))rHDL. At 24 hours postinfusion, acute vascular inflammation was induced by inserting a nonocclusive, periarterial carotid collar. The animals were euthanized 24 hours after the insertion of the collar. The collars caused intima/media neutrophil infiltration and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). ApoA-I(N) infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-I(Glyc in vitro) infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-I(Glyc in vivo) did not inhibit neutrophil infiltration or adhesion molecule expression. (A-I(Glyc in vitro))rHDL also inhibited vascular inflammation less effectively than (A-I(N))rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-kappaB activation and reactive oxygen species formation.
  
  
  CONCLUSIONS
  Nonenzymatic glycation impairs the antiinflammatory properties of apoA-I.
authors.affiliation: Lipid Research Group, The Heart Research Institute, Sydney, New South Wales, Australia.
authors.forename: Estelle
authors.initials: E
authors.lastname: Nobécourt
authors.forename: Fatiha
authors.initials: F
authors.lastname: Tabet
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.forename: Rajesh
authors.initials: R
authors.lastname: Puranik
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Bronwyn E
authors.initials: BE
authors.lastname: Brown
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.forename: David J
authors.initials: DJ
authors.lastname: Bonnet
authors.forename: Linda K
authors.initials: LK
authors.lastname: Curtiss
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000378:metabolism*; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism*; D020212:Carotid Artery Injuries / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006031:Glycosylation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007263:Infusions, Parenteral; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D010713:Phosphatidylcholines / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011765:Pyruvaldehyde / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I; D020672:I-kappa B Proteins; D008075:Lipoproteins, HDL; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D011765:Pyruvaldehyde