Deleterious effect of glycation on the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation.
Fiche publication
Date publication
novembre 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr VERGES Bruno
Tous les auteurs :
Brindisi MC, Duvillard L, Monier S, Verges B, Persegol L
Lien Pubmed
Résumé
BACKGROUND: Contrary to high-density lipoprotein (HDL) from normolipidaemic and normoglycaemic subjects, HDL from diabetic patients loses its ability to reverse the inhibition of vasorelaxation induced by oxidized low-density lipoprotein (LDL). The aim of this study was to analyze the role of glycation, a major abnormality observed in diabetes, on the impairment of the vasorelaxant effect of HDL. METHODS: HDL from healthy subjects was glycated in vitro by incubation in glucose 200 mmol/L for 3 days. Vasoreactivity was evaluated by the relaxation response to acetylcholine of rabbit aorta rings pre-contracted with noradrenaline, before and after 2 h incubation with or without different lipoprotein fractions (Krebs buffer, oxidized LDL, normal or glycated HDL alone and with oxidized LDL). RESULT: The fructosamine/apolipoprotein AI ratio was significantly increased in glycated HDL compared with native HDL (53.63 +/- 7.91 vs 18.51 +/- 4.10 micromol/g; p < 0.05). Oxidized LDL inhibited endothelium-dependent vasodilation compared with Krebs buffer [maximal relaxation (Emax) = 53.15 +/- 6.50 vs 98.67 +/- 2.07%, p < 0.001]. Native HDL was able to counteract the oxidized LDL-induced inhibition of vasorelaxation (Emax = 76.93 +/- 5.41 vs 53.15 +/- 6.50%, p < 0.001). On the other hand, glycated HDL had no effect on oxidized LDL-induced inhibition of endothelium vasorelaxation compared with incubation with oxidized LDL alone (Emax = 52.98 +/- 2.07 vs 53.15 +/- 6.50%, not significant). CONCLUSION: Glycation of HDL induces the loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation, this is likely contributing to the impairment of antiatherogenic properties of HDL in diabetic patients.
Référence
Diabetes Metab Res Rev. 2013 Nov;29(8):618-23