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.
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.
Tailleux
Anne
A
Département de Recherches sur l'Athérosclérose, Inserm U545, Institut Pasteur de Lille, Lille, France.
Gozzo
Andrea
A
Torpier
Gérard
G
Martin-Nizard
Françoise
F
Bonnefont-Rousselot
Dominique
D
Lemdani
Mohamed
M
Furman
Christophe
C
Foricher
Rachel
R
Chevé
Gwenaël
G
Yous
Saïd
S
Micard
Florence
F
Bordet
Régis
R
Gardes-Albert
Monique
M
Lesieur
Daniel
D
Teissier
Elisabeth
E
Fruchart
Jean-Charles
JC
Fiévet
Catherine
C
Duriez
Patrick
P
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
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