Nonenzymatic Glycation Impairs the Antiinflammatory Properties of Apolipoprotein A-I

OBJECTIVE: To investigate the effects of non-enzymatic glycation on the anti-inflammatory 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 non-enzymatically glycated by incubation with methylglyoxal (apoA-I(Glyc in vitro)), non-enzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I(Glyc in vivo)), discoidal reconstituted HDL containing phosphatidylcholine and apoA-I(N), (A-I(N))rHDL, or apoA-I(Glyc in vitro), (A-I(Glyc in vitro))rHDL. At 24 h post-infusion, acute vascular inflammation was induced by inserting a non-occlusive, periarterial carotid collar. The animals were sacrificed 24 h post-collar insertion. 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 anti-inflammatory properties of non-enzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-κB activation and reactive oxygen species formation. CONCLUSION: Non-enzymatic glycation impairs the anti-inflammatory properties of apoA-I