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Role of Beta-adrenergic Receptors and Sirtuin Signaling in the Heart During Aging, Heart Failure, and Adaptation to Stress

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Abstract

In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (β-ARs), mainly the beta 1 (β1-AR) and beta 2 (β2-AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The β2-ARs can also couple to the Gi protein that counterbalances the effect of the Gs protein on cyclic adenosine monophosphate production and activates the phosphatidylinositol 3-kinase (PI3K)–Akt signaling pathway. In several cardiovascular disorders, including heart failure, as well as in aging and in animal models of environmental stress, a reduction in the β1/β2-AR ratio and activation of the β2-AR-Gi-PI3K–Akt signaling pathway have been observed. Recent studies have shown that sirtuins modulate certain organic processes, including the cellular stress response, through activation of the PI3K–Akt signaling pathway and of downstream molecules such as p53, Akt, HIF1-α, and nuclear factor-kappa B. In the heart, SIRT1, SIRT3, and β2-ARs are crucial to the regulation of the cardiomyocyte energy metabolism, oxidative stress, reactive oxygen species production, and autophagy. SIRT1 and the β2-AR-Gi complex also control signaling pathways of cell survival and death. Here, we review the role played by β2-ARs and sirtuins during aging, heart failure, and adaptation to stress, focusing on the putative interplay between the two. That relationship, if proven, merits further investigation in the context of cardiac function and dysfunction.

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Acknowledgements

The authors acknowledge the financial support provided by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo Research Foundation; Grants 2012/21990-6 and 2016/20777-8), the Fundação de Amparo à Pesquisa do Espírito Santo (FAPES, Foundation for the Support of Research in the State of Espírito Santo; Grant 74087886), and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development; Grant 424114/2016-0).

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Authors and Affiliations

  1. Laboratory of Stress Biology, Department of Biosciences, Campus Baixada Santista, Universidade Federal de São Paulo (UNIFESP), Santos, Brazil

    Regina Celia Spadari, Ana Elisa T. Saturi de Carvalho, Daniela Ortolani & Andre Luiz de Moura

  2. Center for Neurosciences and Cell Biology (CNC) and School of Pharmacy, University of Coimbra, Coimbra, Portugal

    Claudia Cavadas

  3. Department of Physiological Science, Universidade Federal Do Espírito Santo (HUCAM, UFES), Vitória, Brazil

    Daniela Ortolani & Paula Frizera Vassalo

  4. University Hospital Cassiano Antônio de Moraes, Universidade Federal Do Espírito Santo (HUCAM, UFES), Vitória, Brazil

    Paula Frizera Vassalo

  5. Departamento de Biociências / Campus Baixada Santista, UNIFESP, Rua Silva Jardim 136, Santos, SP, 11015-020, Brazil

    Regina Celia Spadari

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  1. Regina Celia Spadari
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  2. Claudia Cavadas
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  6. Paula Frizera Vassalo
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Contributions

RCS was responsible for the manuscript concept and design, coordinated the editorial plan, and contributed to manuscript writing and final edition. CC contributed to the manuscript concept and writing, and took part in manuscript's final edition. PFV contributed to the manuscript writing and edition. DO and ALM contributed to the literature search and selection. All authors critically reviewed content and approved the final version of this publication.

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Correspondence to Regina Celia Spadari.

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Spadari, R.C., Cavadas, C., de Carvalho, A.E.T.S. et al. Role of Beta-adrenergic Receptors and Sirtuin Signaling in the Heart During Aging, Heart Failure, and Adaptation to Stress. Cell Mol Neurobiol 38, 109–120 (2018). https://doi.org/10.1007/s10571-017-0557-2

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