Overexpression of antioxidant enzymes in ApoE-deficient mice suppresses Benzo(a)pyrene-accelerated atherosclerosis
| Autor: | ZhongMao Guo, Yanfeng Zhao, LiChun Zhou, Ze-Fen Wang, Xinghua Lin, L. Jackson Roberts, Hong Yang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Apolipoprotein E
animal structures Aortic Diseases Mice Transgenic Monocytes Article Superoxide dismutase Lipid peroxidation Mice chemistry.chemical_compound Apolipoproteins E Superoxide Dismutase-1 Benzo(a)pyrene Cell Adhesion polycyclic compounds Animals Humans Cells Cultured Mice Knockout chemistry.chemical_classification Reactive oxygen species biology Superoxide Dismutase Superoxide Endothelial Cells Atherosclerosis Catalase Lipids Molecular biology Up-Regulation Mice Inbred C57BL Disease Models Animal chemistry Biochemistry biology.protein Dismutase Lipid Peroxidation Reactive Oxygen Species Cardiology and Cardiovascular Medicine Cell Adhesion Molecules |
| Zdroj: | Atherosclerosis. 207:51-58 |
| ISSN: | 0021-9150 |
| Popis: | The carcinogenic polycylic aromatic hydrocarbon, benzo(a)pyrene (BaP), has been shown to generate reactive oxygen species (ROS) and accelerate the development of atherosclerosis. To assess the causal role of BaP-generated ROS in this process, we evaluated atherosclerotic metrics in apolipoprotein E-deficient (ApoE(-/-)) mice with or without overexpression of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and/or catalase. Without BaP, aortic atherosclerotic lesions were smaller in ApoE(-/-) mice overexpressing catalase or both Cu/Zn-SOD and catalase than in those overexpressing neither or Cu/Zn-SOD only. After treating with BaP or vehicle for 24 weeks, mean lesion sizes in the aortic tree and aortic root of ApoE(-/-) mice were increased by approximately 60% and 40%, respectively. BaP also increased the levels of oxidized lipids in the aortic tree of ApoE(-/-) mice and increased the frequency of advanced lesions. In contrast, BaP did not significantly alter lipid peroxidation levels or atherosclerotic lesions in the aortas of ApoE(-/-) mice overexpressing Cu/Zn-SOD and/or catalase. Overexpression of Cu/Zn-SOD and/or catalase also inhibited BaP-induced expression of cell adhesion molecules in aortas and endothelial cells, and reduced BaP-induced monocyte adhesion to endothelial cells. These observations, together with the functions of catalase and Cu/Zn-SOD to scavenge hydrogen peroxide and superoxide anions, implicate a causal role of ROS in the pathogenesis of BaP-induced atherosclerosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect