Deficiency of Glutathione Peroxidase-1 Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 27 Số 4 - Trang 850-857 - 2007
Michael Torzewski1, Viola Ochsenhirt1, Andrei L. Kleschyov1, Matthias Oelze1, Andreas Daiber1, Huige Li1, Heidi Rossmann1, Sotirios Tsimikas1, Kurt Reifenberg1, Fei Cheng1, Hans‐Anton Lehr1, Stefan Blankenberg1, Thomas Münzel1, Karl J. Lackner1
1From the Institute of Clinical Chemistry and Laboratory Medicine (M.T., V.O., F.C., H.R., K.J.L.), Department of Medicine II (A.L.K., M.O., A.D., S.B., T.M.), Department of Pharmacology (H.L., U.F.), Central Laboratory Animal Facility (K.R.), Johannes Gutenberg University, Mainz, Germany; Division of Cardiology (S.T), University of California, San Diego, Calif; Institute Universitaire de Pathologie (H-A.L.), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1006/abbi.2001.2295

10.1016/0891-5849(87)90032-3

10.1016/0076-6879(95)52007-4

10.1007/PL00000664

1988, Basic Life Sci, 49, 663

10.1016/S0891-5849(99)00177-X

10.1016/S0092-8674(01)00238-0

10.1056/NEJMoa030535

10.1074/jbc.272.26.16644

10.1161/atvb.21.7.1131

10.1152/ajpheart.00598.2001

10.1161/01.atv.0000041629.92741.dc

10.1161/01.cir.0000026820.87824.6a

10.1161/circ.97.19.1930

10.1161/01.res.0000082978.92494.b1

10.1016/j.bbrc.2005.10.098

2006, J Lipid Res, 28, 28.

1967, J Lab Clin Med, 70, 158

10.1038/28204

10.1177/002215549704501112

10.1177/002215549904700113

10.1161/circ.104.16.1887

10.1194/jlr.M400467-JLR200

10.1161/atvb.18.12.1972

10.1172/JCI4533

10.1161/atvb.21.1.95

10.1161/01.atv.0000034022.11764.ec

10.1152/ajpcell.2001.280.1.C53

10.1161/01.cir.0000109701.77059.e9

10.1002/jcp.10119

10.2337/diabetes.54.10.2882

10.1074/jbc.M503296200

10.1152/physrev.00047.2003

10.1097/00041433-200010000-00008

10.2337/diabetes.53.12.3217

10.1161/atvb.17.9.1734

10.1089/15230860152409040

10.1161/01.res.0000149564.49410.0d

10.1161/atvb.21.9.1477

10.1161/01.cir.0000031331.05368.9d

10.1161/01.cir.0000023921.93743.89

10.1161/atvb.20.6.1529

10.1161/circ.101.11.1234

10.1161/01.res.0000188210.72062.10

10.1161/01.atv.0000034706.24149.95

10.1001/jama.293.11.1338

Thông tin
Thông tin xuất bản

Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 27 Số 4

850-857

Thông tin tác giả