Deleterious effect of glycation on the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation

作者：Brindisi M C^*; Duvillard L; Monier S; Verges B; Persegol L

来源：Diabetes/Metabolism Research and Reviews, 2013, 29(8): 618-623.

DOI：10.1002/dmrr.2434

• HDL
• glycation
• oxidized LDL
• diabetes mellitus
• vasorelaxation

BackgroundContrary 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. %26lt;br%26gt;MethodsHDL from healthy subjects was glycated in vitro by incubation in glucose 200mmol/L for 3days. Vasoreactivity was evaluated by the relaxation response to acetylcholine of rabbit aorta rings pre-contracted with noradrenaline, before and after 2h incubation with or without different lipoprotein fractions (Krebs buffer, oxidized LDL, normal or glycated HDL alone and with oxidized LDL). %26lt;br%26gt;ResultThe fructosamine/apolipoprotein AI ratio was significantly increased in glycated HDL compared with native HDL (53.637.91 vs 18.51 +/- 4.10 mu mol/g; p%26lt;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%26lt;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%26lt;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). %26lt;br%26gt;ConclusionGlycation 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.

• 出版日期2013-11