Titre
Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Torzewski, M.
Auteure/Auteur
Ochsenhirt, V.
Auteure/Auteur
Kleschyov, A. L.
Auteure/Auteur
Oelze, M.
Auteure/Auteur
Daiber, A.
Auteure/Auteur
Li, H.
Auteure/Auteur
Rossmann, H.
Auteure/Auteur
Tsimikas, S.
Auteure/Auteur
Reifenberg, K.
Auteure/Auteur
Cheng, F.
Auteure/Auteur
Lehr, H. A.
Auteure/Auteur
Blankenberg, S.
Auteure/Auteur
Forstermann, U.
Auteure/Auteur
Munzel, T.
Auteure/Auteur
Lackner, K. J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1524-4636
Statut éditorial
Publié
Date de publication
2007
Volume
27
Numéro
4
Première page
850
Dernière page/numéro d’article
857
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
BACKGROUND: We have recently demonstrated that activity of red blood cell glutathione peroxidase-1 is inversely associated with the risk of cardiovascular events in patients with coronary artery disease. The present study analyzed the effect of glutathione peroxidase-1 deficiency on atherogenesis in the apolipoprotein E-deficient mouse. METHODS AND RESULTS: Female apolipoprotein E-deficient mice with and without glutathione peroxidase-1 deficiency were placed on a Western-type diet for another 6, 12, or 24 weeks. After 24 weeks on Western-type diet, double-knockout mice (GPx-1(-/-)ApoE(-/-)) developed significantly more atherosclerosis than control apolipoprotein E-deficient mice. Moreover, glutathione peroxidase-1 deficiency led to modified atherosclerotic lesions with increased cellularity. Functional experiments revealed that glutathione peroxidase-1 deficiency leads to increased reactive oxygen species concentration in the aortic wall as well as increased overall oxidative stress. Peritoneal macrophages from double-knockout mice showed increased in vitro proliferation in response to macrophage-colony-stimulating factor. Also, we found lower levels of bioactive nitric oxide as well as increased tyrosine nitration as a marker of peroxynitrite production. CONCLUSIONS: Deficiency of an antioxidative enzyme accelerates and modifies atherosclerotic lesion progression in apolipoprotein E-deficient mice
Sujets
PID Serval
serval:BIB_E0AE7A0E32AB
PMID
Open Access
Oui
Date de création
2008-01-29T17:34:34.311Z
Date de création dans IRIS
2025-05-21T05:49:24Z