Nonenzymatic glycation impairs the antiinflammatory properties of apolipoprotein A-I

Research output: Contribution to journalJournal articlepeer-review

  • Estelle Nobécourt
  • Fatiha Tabet
  • Gilles Lambert
  • Rajesh Puranik
  • Shisan Bao
  • Ling Yan
  • Davies, Michael J.
  • Bronwyn E Brown
  • Alicia J Jenkins
  • Gregory J Dusting
  • David J Bonnet
  • Linda K Curtiss
  • Philip J Barter
  • Kerry-Anne Rye

OBJECTIVE: The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I.

METHODS AND 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.

Original languageEnglish
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number4
Pages (from-to)766-72
Number of pages7
Publication statusPublished - Apr 2010
Externally publishedYes

    Research areas

  • Active Transport, Cell Nucleus, Animals, Anti-Inflammatory Agents, Apolipoprotein A-I, Carotid Arteries, Carotid Artery Injuries, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Disease Models, Animal, Glycosylation, Humans, I-kappa B Proteins, Inflammation, Infusions, Parenteral, Intercellular Adhesion Molecule-1, Lipoproteins, HDL, NF-kappa B, Neutrophil Infiltration, Phosphatidylcholines, Phosphorylation, Protein Processing, Post-Translational, Pyruvaldehyde, Rabbits, Reactive Oxygen Species, Time Factors, Vascular Cell Adhesion Molecule-1

ID: 129670118