title: Overexpression of antioxidant enzymes in ApoE-deficient mice suppresses benzo(a)pyrene-accelerated atherosclerosis.
abstract: 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.
authors.affiliation: Department of Cardiovascular Biology, Meharry Medical College, Nashville, TN 37208, United States. Hyang@mmc.edu
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: LiChun
authors.initials: L
authors.lastname: Zhou
authors.forename: Zefen
authors.initials: Z
authors.lastname: Wang
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Xinghua
authors.initials: X
authors.lastname: Lin
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: ZhongMao
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001564:Benzo(a)pyrene; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology; D006801:Humans; D015227:Lipid Peroxidation; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D008055:Lipids; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D001564:Benzo(a)pyrene; D002374:Catalase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1