Oxidation-induced loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on vasorelaxation.
Fiche publication
Date publication
novembre 2015
Journal
Heart and vessels
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DUVILLARD Laurence, Pr VERGES Bruno, Mr MONIER Serge, Dr PAIS DE BARROS Jean-Paul
Tous les auteurs :
Perségol L, Brindisi MC, Rageot D, Pais de Barros JP, Monier S, Vergès B, Duvillard L
Lien Pubmed
Résumé
Several current diseases are associated with an increase in the oxidation of HDL, which is likely to impair their functionality. Our aim was to identify whether oxidation could change the protective effect of HDL against the deleterious effect on vasoreactivity induced by oxidative stress. HDL from healthy subjects were oxidized in vitro by Cu(2+), and the ability of oxidized HDL to counteract the inhibitory effect of oxidized LDL on acetylcholine-induced vasodilation was tested on isolated rabbit aorta rings. Oxidation of HDL was evidenced by the increase in the 7-oxysterols/cholesterol ratio (3.20 ± 1.12 vs 0.02 ± 0.01 % in native HDL, p < 0.05). Oxidized LDL inhibited endothelium-dependent vasodilation (E max = 50.2 ± 5.0 vs 92.5 ± 1.7 % for incubation in Kreb's buffer, p < 0.05) and native HDL counteracted this inhibition (E max = 72.4 ± 4.8 vs 50.2 ± 5.0 % p < 0.05). At the opposite, oxidized HDL had no effect on oxidized LDL-induced inhibition on endothelium-dependent vasorelaxation (E max = 53.7 ± 4.8 vs 50.2 ± 5.0 %, NS). HDL oxidation is associated with a decreased ability of HDL to remove 7-oxysterols from oxidized LDL. In conclusion, these results show that oxidation of HDL induces the loss of their protective effect against endothelial dysfunction, which could promote atherosclerosis in diseases associated with increased oxidative stress.
Mots clés
Acetylcholine, therapeutic use, Animals, Aorta, drug effects, Female, Humans, In Vitro Techniques, Lipoproteins, HDL, blood, Lipoproteins, LDL, blood, Male, Middle Aged, Oxidative Stress, drug effects, Rabbits, Vasodilation, drug effects
Référence
Heart Vessels. 2015 Nov;30(6):845-9