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cAMP Compartmentalisation and Hypertrophy of the Heart: ‘Good’ Pools of cAMP and ‘Bad’ Pools of cAMP Coexist in the Same Cardiac Myocyte

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Microdomains in the Cardiovascular System

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 3))

Abstract

Pathological growth of cardiomyocytes (hypertrophy) is a major determinant of heart failure, a leading medical cause of mortality worldwide. Initially, cardiac hypertrophy is a compensatory response aimed at increasing cardiac output. However, prolonged cardiac hypertrophy progresses to contractile dysfunction, cardiac decompensation, and finally to heart failure. Although chronic elevation of cardiac cAMP leads to pathologic sequelae, enhancement of particular aspects of cAMP/PKA signalling benefits the failing heart, suggesting that different components of this pathway may have different consequences on cardiac hypertrophy and failure. The finding that cAMP signalling is compartmentalised and that distinct, spatially segregated pools of cAMP mediate different functional effects in the heart may provide a rationale for what appear to be contrasting effects of this pathway on cardiac physiology and pathophysiology. In this chapter, we review some of the evidence in support of compartmentalisation of cAMP/PKA signalling, and we summarise recent findings indicating that distinct pools of cAMP, under the control of different phosphodiesterases, have opposing effects on cardiac myocytes hypertrophic growth. The relevance of these findings for the potential development of innovative approaches to reverse the course of ventricular remodelling is also briefly discussed.

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Acknowledgements

This study was supported by the British Heart Foundation (PG/10/75/28537 and RG/12/3/29423) and the BHF Centre of Research Excellence, Oxford (RE/08/004) to M. Z.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cardiovascular Division, King’s College London BHF Centre of Research Excellence, London, UK

    Anna Zoccarato

  2. Department of Physiology, Anatomy and Genetics, BHF Centre of Research Excellence, University of Oxford, Sherrington Building, Parks Road, Oxford, OX1 3QX, UK

    Manuela Zaccolo

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  1. Anna Zoccarato
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Correspondence to Manuela Zaccolo .

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Editors and Affiliations

  1. Institute of Experimental Cardiovascular Research, University Medical Center, Hamburg-Eppendorf, Germany

    Viacheslav Nikolaev

  2. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

    Manuela Zaccolo

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Zoccarato, A., Zaccolo, M. (2017). cAMP Compartmentalisation and Hypertrophy of the Heart: ‘Good’ Pools of cAMP and ‘Bad’ Pools of cAMP Coexist in the Same Cardiac Myocyte. In: Nikolaev, V., Zaccolo, M. (eds) Microdomains in the Cardiovascular System. Cardiac and Vascular Biology, vol 3. Springer, Cham. https://doi.org/10.1007/978-3-319-54579-0_7

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