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dc.contributor.authorKirk, Elizabeth A.en_US
dc.contributor.authorHeinecke, Jay W.en_US
dc.contributor.authorLeBoeuf, Renée C.en_US
dc.date.accessioned2010-04-21T15:55:37Z
dc.date.available2010-04-21T15:55:37Z
dc.date.issued2001-06-15en_US
dc.identifier.citationKirk EA, Heinecke JW, LeBoeuf RC. Iron overload diminishes atherosclerosis in apoE-deficient mice. J Clin Invest. 2001;107(12):1545-1553.en_US
dc.identifier.other10.1172/JCI7664en_US
dc.identifier.urihttp://www.jci.org/articles/view/7664en_US
dc.identifier.urihttp://hdl.handle.net/1773/15771
dc.description.abstractIt has been proposed that elevated levels of tissue iron increase the risk for atherosclerosis, perhaps by favoring the formation of pro-atherogenic oxidized LDL. Working with apoE-deficient (apoE–/–) mice, which do not require a high-fat diet to develop atherosclerosis, we compared the effects of standard diet (0.02% iron) or a 2% carbonyl iron diet. After 24 weeks, mice fed the 2% carbonyl iron diet had twice as much iron in their plasma, a ninefold increase in bleomycin-detectable free iron in their plasma, and ten times as much iron in their livers as control mice. Dietary iron overload caused a modest (30%) rise in plasma triglyceride and cholesterol. Nevertheless, this regimen did not exacerbate, but rather reduced the severity of atherosclerosis by 50%, and it failed to elevate hepatic levels of heme oxygenase mRNA, which is induced by many different oxidative insults in vitro. Moreover, hepatic levels of protein-bound dityrosine and ortho-tyrosine, two markers of metal-catalyzed oxidative damage in vitro, failed to rise in iron-overloaded animals. Our observations suggest that elevated serum and tissue levels of iron are not atherogenic in apoE–/– mice. Moreover, they call into question the hypothesis that elevated levels of tissue iron promote LDL oxidation and oxidative stress in vivo.en_US
dc.description.sponsorshipNIH grants DK-02456, HL-52848, AG-15013, DK-56341, and RR-00954, the American Heart Association, and the Pharmacia-Monsanto-Searle/Washington University Biomedical Program.en_US
dc.language.isoen_USen_US
dc.titleIron overload diminishes atherosclerosis in apoE-deficient miceen_US


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