The role of urate and xanthine oxidase in vascular oxidative stress: Future directions

Jacob George, Allan Struthers

    Research output: Contribution to journalArticle

    20 Citations (Scopus)
    227 Downloads (Pure)

    Abstract

    Vascular oxidative stress has been shown to be a potent factor in the pathophysiology of endothelial dysfunction. Despite current optimal evidence-based therapy, mortality from various cardiovascular disorders remains high. The search for newer, novel ways of attenuating endothelial dysfunction has yielded several new and exciting possibilities, one of which is the manipulation of urate levels using xanthine oxidase inhibitors. Agents such as allopurinol have shown marked improvements in vascular endothelial function in various cohorts at risk of cardiovascular events. Most of the evidence so far comes from smaller mechanistic studies. The few large randomized controlled trials have failed to show any significant mortality benefit using these agents. This article highlights the potential avenues of further research such as dose-response, and the potential for these agents to regress left ventricular hypertrophy. The role of newer agents such as febuxostat and oxypurinol are discussed as well as potential reasons why some of the current newer agents have failed to live up to the promising early-phase data. It is crucial that these remaining questions surrounding urate, xanthine oxidase and the role of various agents that affect this important oxidative stress-generating system are answered, and therefore these promising agents should not be discarded prematurely.
    Original languageEnglish
    Pages (from-to)799-803
    Number of pages5
    JournalTherapeutics and Clinical Risk Management
    Volume5
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2009

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