title: Deleterious effect of glycation on the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation.
abstract: 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).
  
  
  RESULTS
  The fructosamine/apolipoprotein AI ratio was significantly increased in glycated HDL compared with native HDL (53.63 ± 7.91 vs 18.51 ± 4.10 µmol/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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM Research Center 866, Dijon, France; University of Burgundy, IFR100, Dijon, France; Service de Diabétologie, Endocrinologie, Maladies Metabolique, CHU du Bocage, Dijon, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Brindisi
authors.forename: L
authors.initials: L
authors.lastname: Duvillard
authors.forename: S
authors.initials: S
authors.lastname: Monier
authors.forename: B
authors.initials: B
authors.lastname: Vergès
authors.forename: L
authors.initials: L
authors.lastname: Perségol
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D064368:Healthy Volunteers; D006801:Humans; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D011817:Rabbits; D014664:Vasodilation / Q000502:physiology*
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
keywords: HDL; diabetes mellitus; glycation; oxidized LDL; vasorelaxation