Daily melatonin supplementation in mice increases atherosclerosis in proximal aorta.
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.
Tailleux
Anne
A
Département d'Athérosclérose, Inserm U545, Institut Pasteur, 1 rue du Pr Calmette, 59019 Lille, France.
Torpier
Gérard
G
Bonnefont-Rousselot
Dominique
D
Lestavel
Sophie
S
Lemdani
Mohamed
M
Caudeville
Bernadette
B
Furman
Christophe
C
Foricher
Rachel
R
Gardes-Albert
Monique
M
Lesieur
Daniel
D
Rolando
Christian
C
Teissier
Elisabeth
E
Fruchart
Jean-Charles
JC
Clavey
Véronique
V
Fievet
Catherine
C
Duriez
Patrick
P
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
D000975:Antioxidants; D001055:Apolipoproteins B; D008074:Lipoproteins; D002784:Cholesterol; D008550:Melatonin; C012365:6-hydroxymelatonin