The antioxidant N-acetylcysteine prevents accelerated atherosclerosis in uremic apolipoprotein E knockout mice.

Détails

ID Serval
serval:BIB_666ED0BF9D8F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The antioxidant N-acetylcysteine prevents accelerated atherosclerosis in uremic apolipoprotein E knockout mice.
Périodique
Kidney International
Auteur⸱e⸱s
Ivanovski O., Szumilak D., Nguyen-Khoa T., Ruellan N., Phan O., Lacour B., Descamps-Latscha B., Drüeke T.B., Massy Z.A.
ISSN
0085-2538 (Print)
ISSN-L
0085-2538
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
67
Numéro
6
Pages
2288-2294
Langue
anglais
Résumé
BACKGROUND: Cardiovascular disease is the most frequent cause of mortality in chronic renal failure (CRF). Therefore, it is important to identify appropriate treatment measures. The antioxidant N-acetylcysteine (NAC) has been shown to reduce cardiovascular events in hemodialysis patients. Here we examine a possible direct effect of NAC supplementation on uremia-enhanced atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice.
METHODS: Uremia was induced surgically in 8-week-old female apoE(-/-) mice. Two weeks after creation of CRF mice were randomized to receive either NAC (daily oral gavage with 200 mg/kg for 8 weeks) or placebo. They were compared to a control group of sham-operated apoE(-/-) mice receiving placebo. After 8 weeks of treatment, the mice were sacrificed, and the cross-section surface area of atherosclerotic plaques was measured in aortic root and descending aorta.
RESULTS: At 10 weeks following surgery, atherosclerotic lesions were significantly larger in uremic apoE(-/-) mice than in nonuremic controls. This accelerated atherosclerosis was associated with an increase in aortic nitrotyrosine expression and collagen plaque content. NAC treatment inhibited the progression of atherosclerotic lesions and plaque collagen content compared with placebo treatment. In addition, plaques from NAC-treated uremic animals showed a significant decrease in nitrotyrosine expression whereas the degree of macrophage infiltration was comparable in both uremic groups. There was no difference in mean arterial blood pressure between the three groups.
CONCLUSION: We show for the first time that the antioxidant NAC is capable of reducing atheroma progression, in an animal model of uremia-enhanced atherosclerosis, probably via a decrease in oxidative stress.
Mots-clé
Acetylcysteine/pharmacology, Animals, Antioxidants/pharmacology, Aorta/pathology, Apolipoproteins E/genetics, Apolipoproteins E/physiology, Arteriosclerosis/metabolism, Arteriosclerosis/pathology, Body Weight/drug effects, Collagen/analysis, Female, Mice, Mice, Knockout, Tyrosine/analogs & derivatives, Tyrosine/analysis, Uremia/complications
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/03/2016 17:47
Dernière modification de la notice
20/08/2019 14:22
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