Back
Full-text
Journal article

Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice.

  • Nomura J 1] Pharmaceutical Department Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan [2] Service of Rheumatology, Department of l'Appareil Locomoteur, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
  • Busso N Service of Rheumatology, Department of l'Appareil Locomoteur, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
  • Ives A Service of Rheumatology, Department of l'Appareil Locomoteur, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
  • Matsui C Pharmaceutical Department Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • Tsujimoto S Pharmaceutical Department Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • Shirakura T Pharmaceutical Department Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • Tamura M Pharmaceutical Department Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • Kobayashi T Pharmaceutical Department Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • So A Service of Rheumatology, Department of l'Appareil Locomoteur, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
  • Yamanaka Y Pharmaceutical Department Research Laboratories, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
Show more…
  • 2014-04-02
Published in:
  • Scientific reports. - 2014
Animals
Aorta
Apolipoproteins E
Atherosclerosis
Body Weight
Cholesterol
Cytokines
Disease Models, Animal
Endothelial Cells
Febuxostat
Gout Suppressants
Inflammation
L-Lactate Dehydrogenase
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Oxidative Stress
Plaque, Atherosclerotic
Reactive Oxygen Species
Thiazoles
Xanthine Oxidase
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/43154
Statistics
Document views: 27 File downloads:
  • Full-text: 0