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NADPH oxidases and cardiac remodelling

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Abstract

A heart under chronic stress undergoes cardiac remodelling, a process that comprises structural and functional changes including cardiomyocyte hypertrophy, interstitial fibrosis, contractile dysfunction, cell death and ventricular dilatation. Reactive oxygen species (ROS)-dependent modulation of intracellular signalling is implicated in the development of cardiac remodelling. Among the different ROS sources that are present in the heart, NADPH oxidases (NOXs) are particularly important in redox signalling. NOX isoforms are expressed in multiple cell types including cardiomyocytes, fibroblasts, endothelial cells and inflammatory cells—with the two main isoforms expressed in the heart being NOX2 and NOX4. Recent studies indicate that NOX-dependent signalling is involved in the development of cardiomyocyte hypertrophy, interstitial fibrosis and post-MI remodelling. NOXs may also be involved in the genesis of contractile dysfunction and myocyte apoptosis. Here, we review the main effects of NOXs in the pathogenesis of cardiac remodelling and the redox-sensitive signalling pathways that underlie these effects. The elucidation of mechanisms involved in NOX-dependent regulation of cardiac remodelling may lead to new therapeutic targets for heart failure.

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Acknowledgments

The authors’ work is supported by the British Heart Foundation (RG/08/011/25922, CH/99001; RE/08/003), a Leducq Foundation Transtlantic Network of Excellence Award, and EU FP6 grant LSHM-CT-2005-018833 (EUGeneHeart).

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  1. Cardiovascular Division, King’s College London British Heart Foundation Centre, London, SE5 9PJ, UK

    Adam Nabeebaccus, Min Zhang & Ajay M. Shah

  2. Cardiovascular Division, The James Black Centre, King’s College London, 125 Coldharbour Lane, London, SE5 9NU, UK

    Adam Nabeebaccus

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  1. Adam Nabeebaccus
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Correspondence to Ajay M. Shah.

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Nabeebaccus, A., Zhang, M. & Shah, A.M. NADPH oxidases and cardiac remodelling. Heart Fail Rev 16, 5–12 (2011). https://doi.org/10.1007/s10741-010-9186-2

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