Publication

Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice

Journal Paper/Review - Apr 1, 2007

PubMed
Doi

Citation
Torzewski M, Münzel T, Förstermann U, Blankenberg S, Lehr H, Cheng F, Reifenberg K, Tsimikas S, Rossmann H, Li H, Daiber A, Oelze M, Kleschyov A, Ochsenhirt V, Lackner K. Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2007; 27:850-7.
Type
Journal Paper/Review (English)
Journal
Arterioscler Thromb Vasc Biol 2007; 27
Publication Date
Apr 1, 2007
Issn Electronic
1524-4636
Pages
850-7
Brief description/objective

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.