Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance

Konstantinos Tziomalos, Joshua M. Hare

Research output: Contribution to journalArticle

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 : a journal and virtual library
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

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Xanthine Dehydrogenase
Oxidation-Reduction
Cardiovascular system
Excitation Contraction Coupling
Nitric Oxide Synthase Type I
Oxidative stress
Myofibrils
Sarcoplasmic Reticulum
Cardiovascular System
Uric Acid
Mountings
Cardiac Myocytes
Hypertrophy
Reactive Oxygen Species
Nitric Oxide
Oxidative Stress
Heart Failure
Apoptosis
Calcium
Enzymes

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)

Cite this

Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance. / Tziomalos, Konstantinos; Hare, Joshua M.

In: Frontiers in bioscience : a journal and virtual library, Vol. 14, No. 1, 01.01.2009, p. 237-262.

Research output: Contribution to journalArticle

Tziomalos, Konstantinos ; Hare, Joshua M. / Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance. In: Frontiers in bioscience : a journal and virtual library. 2009 ; Vol. 14, No. 1. pp. 237-262.
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