title: Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E.
abstract: Oxidative stress has been suggested to potentiate atherogenesis. However, studies that have investigated the effect of antioxidants on atherosclerosis showed inconsistent results, ie, atherosclerosis was either retarded or not changed by dietary antioxidants. This report directly examined the effect of overexpressing Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and/or catalase on atherosclerosis and lipid peroxidation in mice lacking apolipoprotein E (ApoE-/-). Based on lipid staining of the en face of the aorta tree and the serial sections of the proximal aorta, ApoE-/- mice overexpressing catalase or both Cu/Zn-SOD and catalase had smaller and relatively early stages of atherosclerotic lesions (eg, foam cells and free lipids) when compared with ApoE-/- mice, who developed more advanced lesions (eg, fibrous caps and acellular areas). In addition, the retarded development of atherosclerosis was correlated with a reduced F2-isoprostanes in the plasma and aortas in ApoE-/- mice overexpressing catalase or both Cu/Zn-SOD and catalase. In contrast, the levels of F2-isoprostanes and atherosclerosis in the ApoE-/- mice overexpressing Cu/Zn-SOD alone were comparable to ApoE-/- control mice. These observations implied that endogenously produced hydrogen peroxide, but not superoxide anions, contributed to the formation of oxidized lipids and the development of atherosclerosis in ApoE-/- mice.
authors.affiliation: Department of Pathology, Meharry Medical College, Nashville, Tenn 37208, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Ming Jian
authors.initials: MJ
authors.lastname: Shi
authors.forename: Li Chun
authors.initials: LC
authors.lastname: Zhou
authors.forename: Billy R
authors.initials: BR
authors.lastname: Ballard
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Zhong Mao
authors.initials: ZM
authors.lastname: Guo
mesh_terms: D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002374:Catalase / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D004790:Enzyme Induction; D028441:F2-Isoprostanes / Q000032:analysis; D005487:Foam Cells / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000235:genetics; D015227:Lipid Peroxidation; D008055:Lipids / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D028441:F2-Isoprostanes; D008055:Lipids; D011993:Recombinant Fusion Proteins; D014280:Triglycerides; D002784:Cholesterol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase