Xanthine Oxidase Inhibition by Febuxostat Attenuates Experimental Atherosclerosis in Mice
書誌事項
- 公開日
- 2014-04-01
- 権利情報
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- https://creativecommons.org/licenses/by/3.0/
- https://creativecommons.org/licenses/by/3.0/
- DOI
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- 10.1038/srep04554
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title><jats:p>Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the arterial wall. Multiple mechanisms participate in the inflammatory process, including oxidative stress. Xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. Here, we show enhanced XO expression in macrophages in the atherosclerotic plaque and in aortic endothelial cells in ApoE<jats:sup>−/−</jats:sup> mice and that febuxostat, a highly potent XO inhibitor, suppressed plaque formation, reduced arterial ROS levels and improved endothelial dysfunction in ApoE<jats:sup>−/−</jats:sup> mice without affecting plasma cholesterol levels. <jats:italic>In vitro</jats:italic>, febuxostat inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages. These results demonstrate that in the atherosclerotic plaque, XO-mediated ROS formation is pro-inflammatory and XO-inhibition by febuxostat is a potential therapy for atherosclerosis.</jats:p>
収録刊行物
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- Scientific Reports
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Scientific Reports 4 (1), 4554-, 2014-04-01
Springer Science and Business Media LLC