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. Methods and results: Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-IN), 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-IGlyc in vivo), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I N, (A-IN)rHDL, or apoA-IGlyc 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-IN infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-IGlyc in vitro infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-IGlyc in vivo did not inhibit neutrophil infiltration or adhesion molecule expression. (A-IGlyc in vitro)rHDL also inhibited vascular inflammation less effectively than (A-IN)rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-κB activation and reactive oxygen species formation. Conclusion: Nonenzymatic glycation impairs the antiinflammatory properties of apoA-I. © 2010 American Heart Association, Inc.