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Novel aspects of ROS signalling in heart failure

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Abstract

Heart failure and many of the conditions that predispose to heart failure are associated with oxidative stress. This is considered to be important in the pathophysiology of the condition but clinical trials of antioxidant approaches to prevent cardiovascular morbidity and mortality have been unsuccessful. Part of the reason for this may be the failure to appreciate the complexity of the effects of reactive oxygen species. At one extreme, excessive oxidative stress damages membranes, proteins and DNA but lower levels of reactive oxygen species may exert much more subtle and specific regulatory effects (termed redox signalling), even on physiological signalling pathways. In this article, we review our current understanding of the roles of such redox signalling pathways in the pathophysiology of heart failure, including effects on cardiomyocyte hypertrophy signalling, excitation–contraction coupling, arrhythmia, cell viability and energetics. Reactive oxygen species generated by NADPH oxidase proteins appear to be especially important in redox signalling. The delineation of specific redox-sensitive pathways and mechanisms that contribute to different components of the failing heart phenotype may facilitate the development of newer targeted therapies as opposed to the failed general antioxidant approaches of the past.

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Acknowledgments

The authors’ work is supported by the British Heart Foundation (RE/08/003); a Fondation Leducq Transatlantic Network of Excellence Award; the Department of Health via a National Institute for Health Research (NIHR) Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust; a Medical Research Council Fellowship to AAN; and a Norwegian Health Association Fellowship to ADH.

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Division of Cardiovascular, King’s College London British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK

    Anne D. Hafstad, Adam A. Nabeebaccus & Ajay M. Shah

  2. Department of Medical Biology, The Cardiovascular Research Group, University of Tromsø, Tromsø, Norway

    Anne D. Hafstad

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  1. Anne D. Hafstad
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  2. Adam A. Nabeebaccus
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  3. Ajay M. Shah
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Correspondence to Ajay M. Shah.

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This article is part of the Topical Collection Novel Perspectives on Heart Failure.

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Hafstad, A.D., Nabeebaccus, A.A. & Shah, A.M. Novel aspects of ROS signalling in heart failure. Basic Res Cardiol 108, 359 (2013). https://doi.org/10.1007/s00395-013-0359-8

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  • DOI: https://doi.org/10.1007/s00395-013-0359-8

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