title: Daily melatonin supplementation in mice increases atherosclerosis in proximal aorta.
abstract: Considerable evidence supports the hypothesis that LDL oxidation plays an important role in atherosclerosis. Even though high melatonin doses inhibit LDL oxidation in vitro, the effect of melatonin on atherosclerosis has never been studied. We have demonstrated that the feeding of hypercholesterolemic mice with an atherogenic diet supplemented with melatonin highly increases the surface of atherosclerotic lesions in the proximal aorta. These observations occur without detectable lipidic or glucidic phenotype alteration. Melatonin treatment increased highly the sensitivity of atherogenic lipoprotein to Cu(2+) and gamma-radiolysis generated oxyradical ex vivo oxidation during the fasting period. Moreover, these altered lipoproteins were less recognized by the LDL receptor metabolic pathway of murine fibroblasts while they transferred many more cholesteryl esters to murine macrophages. This study suggests that caution should be taken as regards high melatonin dosage in hypercholesterolemic patients.
authors.affiliation: Département d'Athérosclérose, Inserm U545, Institut Pasteur, 1 rue du Pr Calmette, 59019 Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.forename: Gérard
authors.initials: G
authors.lastname: Torpier
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: Sophie
authors.initials: S
authors.lastname: Lestavel
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lemdani
authors.forename: Bernadette
authors.initials: B
authors.lastname: Caudeville
authors.forename: Christophe
authors.initials: C
authors.lastname: Furman
authors.forename: Rachel
authors.initials: R
authors.lastname: Foricher
authors.forename: Monique
authors.initials: M
authors.lastname: Gardes-Albert
authors.forename: Daniel
authors.initials: D
authors.lastname: Lesieur
authors.forename: Christian
authors.initials: C
authors.lastname: Rolando
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Teissier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.forename: Véronique
authors.initials: V
authors.lastname: Clavey
authors.forename: Catherine
authors.initials: C
authors.lastname: Fievet
authors.forename: Patrick
authors.initials: P
authors.lastname: Duriez
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001011:Aorta / Q000473:pathology*; D001055:Apolipoproteins B / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism; D008550:Melatonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D010084:Oxidation-Reduction
chemical_list: D000975:Antioxidants; D001055:Apolipoproteins B; D008074:Lipoproteins; D002784:Cholesterol; D008550:Melatonin; C012365:6-hydroxymelatonin