serval:BIB_19E53E138754
Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice.
10.1038/srep04554
000333555500003
24686534
Nomura
J.
author
Busso
N.
author
Ives
A.
author
Matsui
C.
author
Tsujimoto
S.
author
Shirakura
T.
author
Tamura
M.
author
Kobayashi
T.
author
So
A.
author
Yamanaka
Y.
author
article
2014
Scientific Reports
2045-2322
2045-2322
journal
4
4554
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(-/-) mice, and that febuxostat, a highly potent XO inhibitor, suppressed plaque formation, reduced arterial ROS levels and improved endothelial dysfunction in ApoE(-/-) mice without affecting plasma cholesterol levels. In vitro, 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.
eng
60_published
true
peer-reviewed
Publication types: Journal Article
University of Lausanne
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