title: Oxidation-induced loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on vasorelaxation.
abstract: 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.
authors.affiliation: Faculté de Médecine, INSERM U866-Université de Bourgogne, 21000, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Perségol
authors.affiliation: Faculté de Médecine, INSERM U866-Université de Bourgogne, 21000, Dijon, France.|Service d'Endocrinologie et Maladies Métaboliques, CHU, Hôpital du Bocage, 21000, Dijon, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Brindisi
authors.affiliation: Plateforme Lipidomique, Structure Fédérative de Recherche, 21000, Dijon, France.
authors.forename: David
authors.initials: D
authors.lastname: Rageot
authors.affiliation: Plateforme Lipidomique, Structure Fédérative de Recherche, 21000, Dijon, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.affiliation: Faculté de Médecine, INSERM U866-Université de Bourgogne, 21000, Dijon, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Monier
authors.affiliation: Faculté de Médecine, INSERM U866-Université de Bourgogne, 21000, Dijon, France.|Service d'Endocrinologie et Maladies Métaboliques, CHU, Hôpital du Bocage, 21000, Dijon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
authors.affiliation: Faculté de Médecine, INSERM U866-Université de Bourgogne, 21000, Dijon, France. laurence.duvillard@chu-dijon.fr.|Biochimie Médicale, Plateau Technique de Biologie, 2 Rue Angélique Ducoudray, BP 37013, 21070, Dijon Cédex, France. laurence.duvillard@chu-dijon.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
mesh_terms: D000109:Acetylcholine / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D000109:Acetylcholine
keywords: Oxidized HDL; Oxidized LDL; Rabbit aorta rings; Vasorelaxation