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Oxidative Stress and Redox Signalling in Cardiac Remodelling

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Studies on Cardiovascular Disorders

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Abstract

Cardiac remodelling describes the chronic response to stresses such as myocardial infarction (MI) or chronic hypertension, which generally becomes maladaptive over time, leading to deleterious structural and functional alterations and manifesting clinically as chronic heart failure (CHF). Although the underlying mechanisms are multifactorial, a significant body of evidence points to important roles for oxidative stress and redox signalling. Oxidative stress, occurring when excess reactive oxygen species (ROS) cannot be adequately countered by antioxidant defences, triggers cell dysfunction, energetic deficit or cell death. However, ROS may also have more subtle effects in the process of remodelling through specific modulation of redox-sensitive signalling pathways that alter gene and protein expression and function. ROS are generated from many sources including mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases; the last of these appear to be especially important in redox signalling. This chapter discusses recent advances in delineating the contribution of ROS to some of the principal alterations underlying the remodelling process (i.e., cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, contractile dysfunction, and chamber dilatation), with a particular emphasis on the role of NADPH oxidase. A better understanding of redox signalling mechanisms may enable the development of new targeted strategies for the prevention and treatment of adverse cardiac remodelling.

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Acknowledgments

The authors’ work is supported by the British Heart Foundation (RG/08/011/25922 and CVH/99001); the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust; and EU FP6 grant LSHM-CT-2005-018833, EUGeneHeart.

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  1. Cardiovascular Division, King’s College London British Heart Foundation Centre of Research Excellence, London, SE5 9NU, UK

    Min Zhang, Alex Sirker & Ajay M. Shah

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  1. Min Zhang
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  2. Alex Sirker
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  3. Ajay M. Shah
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Correspondence to Ajay M. Shah .

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  1. Physiologisches Institut, Universität Gießen, Aulweg 129, Gießen, 35392, Germany

    Heinrich Sauer

  2. James Black Centre, King's College, London, Coldharbour Lane 125, London, SE5 9NU, United Kingdom

    Ajay M. Shah

  3. Fac. Medicina, Instituto do Coração (INCOR), Universidade de São Paulo, Av. Enéas de Carvalho Aguiar 44, São Paulo, 05403-000, São Paulo, Brazil

    Francisco R. M. Laurindo

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Zhang, M., Sirker, A., Shah, A.M. (2010). Oxidative Stress and Redox Signalling in Cardiac Remodelling. In: Sauer, H., Shah, A., Laurindo, F. (eds) Studies on Cardiovascular Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-600-9_21

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