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Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications

Berry, Cristine E., Hare, Joshua M.·2004·The Journal of Physiology

Abstract

There is substantial evidence that oxidative stress participates in the pathophysiology of cardiovascular disease. Biochemical, molecular and pharmacological studies further implicate xanthine oxidoreductase (XOR) as a source of reactive oxygen species in the cardiovascular system. XOR is a member of the molybdoenzyme family and is best known for its catalytic role in purine degradation, metabolizing hypoxanthine and xanthine to uric acid with concomitant generation of superoxide. Gene expression of XOR is regulated by oxygen tension, cytokines and glucocorticoids. XOR requires molybdopterin, iron–sulphur centres, and FAD as cofactors and has two interconvertible forms, xanthine oxidase and xanthine dehydrogenase, which transfer electrons from xanthine to oxygen and NAD+, respectively, yielding superoxide, hydrogen peroxide and NADH. Additionally, XOR can generate superoxide via NADH oxidase activity and can produce nitric oxide via nitrate and nitrite reductase activities. While a role for XOR beyond purine metabolism was first suggested in ischaemia–reperfusion injury, there is growing awareness that it also participates in endothelial dysfunction, hypertension and heart failure. Importantly, the XOR inhibitors allopurinol and oxypurinol attenuate dysfunction caused by XOR in these disease states. Attention to the broader range of XOR bioactivity in the cardiovascular system has prompted initiation of several randomised clinical outcome trials, particularly for congestive heart failure. Here we review XOR gene structure and regulation, protein structure, enzymology, tissue distribution and pathophysiological role in cardiovascular disease with an emphasis on heart failure.

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Metadata

Authors
Berry, C. E., & Hare, J. M.
Venue
The Journal of Physiology
Publisher
Wiley
Published
2004-03-09
Volume
555
Issue
3
Pages
589-606
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
OpenAlex
W1953423403
Cited by
927
References
18
FWCI
18.74
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. https://app.cochat.ai/papers/10.1113/jphysiol.2003.055913
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Berry, C. E., & Hare, J. M. (2004). Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. The Journal of Physiology. https://doi.org/10.1113/jphysiol.2003.055913

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.