title: Increased susceptibility of low-density lipoprotein to ex vivo oxidation in mice transgenic for human apolipoprotein B treated with 1 melatonin-related compound is not associated with atherosclerosis progression.
abstract: Considerable evidence supports the hypothesis that LDL oxidation has an important role in atherosclerosis. It has been demonstrated that the feeding of hypercholesterolemic mice on an atherogenic diet supplemented with melatonin highly increases the surface of atherosclerotic lesions in aorta and the sensitivity of atherogenic lipoprotein to ex vivo oxidation even though high melatonin doses inhibit lipoprotein oxidation in vitro. A melatonin-related compound (DTBHB: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3,5-di-tert-butyl-4-hydroxybenzamide) has been reported to strongly inhibit lipid peroxidation in vitro. In the present study, DTBHB treatment considerably increased the sensitivity of atherogenic lipoproteins to ex vivo oxidation but did not modify atherosclerotic lesion development in mice. Moreover, DTBHB treatment did not induce detectable lipidic alteration. These data confirm that the capacity of molecules to inhibit atherogenic lipoprotein oxidation in vitro offers no prediction of their capacity to inhibit in vivo atherosclerosis development.
authors.affiliation: Département de Recherches sur l'Athérosclérose, Inserm U545, Institut Pasteur de Lille, Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.forename: Andrea
authors.initials: A
authors.lastname: Gozzo
authors.forename: Gérard
authors.initials: G
authors.lastname: Torpier
authors.forename: Françoise
authors.initials: F
authors.lastname: Martin-Nizard
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lemdani
authors.forename: Christophe
authors.initials: C
authors.lastname: Furman
authors.forename: Rachel
authors.initials: R
authors.lastname: Foricher
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Chevé
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
authors.forename: Florence
authors.initials: F
authors.lastname: Micard
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.forename: Monique
authors.initials: M
authors.lastname: Gardes-Albert
authors.forename: Daniel
authors.initials: D
authors.lastname: Lesieur
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Teissier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.forename: Catherine
authors.initials: C
authors.lastname: Fiévet
authors.forename: Patrick
authors.initials: P
authors.lastname: Duriez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001055:Apolipoproteins B / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology*; D001549:Benzamides / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008550:Melatonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D010084:Oxidation-Reduction
chemical_list: D000975:Antioxidants; D001055:Apolipoproteins B; D001549:Benzamides; D016207:Cytokines; D007211:Indoles; D008055:Lipids; D008077:Lipoproteins, LDL; C470989:N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3,5-di-tert-butyl-4-hydroxybenzamide; D002784:Cholesterol; D008550:Melatonin