Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance

Konstantinos Tziomalos, Joshua M. Hare

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Emerging evidence supports the importance of nitroso-redox balance in the cardiovascular system. Xanthine oxidoreductase (XOR) is a major oxidative enzyme and increased XOR activity, leading to both increased production of reactive oxygen species and uric acid, is implicated in heart failure. Within the heart, XOR activity stimulates cardiomyocyte hypertrophy, apoptosis, and impairs matrix structure. The underpinnings of these derangements can be linked not solely to oxidative stress, but may also involve the process of nitroso-redox imbalance. In this regard, XOR interacts with nitric oxide signaling at numerous levels, including a direct proteinprotein interaction with neuronal nitric oxide synthase (NOS1) in the sarcoplasmic reticulum. Deficiency or translocation of NOS1 away from this microdomain leads to increased activity of XOR, which in turn impairs excitation-contraction coupling and myofilament calcium sensitivity. There is a mounting abundance of preclinical data supporting beneficial effects of inhibiting XOR, but translation to the clinic continues to be incomplete. A growing understanding of XOR and its role in nitrosoredox imbalance has great potential to lead to improved pathophysiologic insights and possibly therapeutic advances.

Original languageEnglish (US)
Pages (from-to)237-262
Number of pages26
JournalFrontiers in Bioscience
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Heart failure
  • Nitric oxide
  • Nitroso-redox imbalance
  • Review
  • S-nitrosylation
  • Xanthine oxidoreductase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

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