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Molecular Medicine

, Volume 20, Issue 1, pp 527–537 | Cite as

Cholinergic Activity as a New Target in Diseases of the Heart

  • Ashbeel Roy
  • Silvia Guatimosim
  • Vania F. Prado
  • Robert Gros
  • Marco A. M. Prado
Review Article

Abstract

The autonomic nervous system is an important modulator of cardiac signaling in both health and disease. In fact, the significance of altered parasympathetic tone in cardiac disease has recently come to the forefront. Both neuronal and nonneuronal cholinergic signaling likely play a physiological role, since modulating acetylcholine (ACh) signaling from neurons or cardiomyocytes appears to have significant consequences in both health and disease. Notably, many of these effects are solely due to changes in cholinergic signaling, without altered sympathetic drive, which is known to have significant adverse effects in disease states. As such, it is likely that enhanced ACh-mediated signaling not only has direct positive effects on cardiomyocytes, but it also offsets the negative effects of hyperadrenergic tone. In this review, we discuss recent studies that implicate ACh as a major regulator of cardiac remodeling and provide support for the notion that enhancing cholinergic signaling in human patients with cardiac disease can reduce morbidity and mortality. These recent results support the idea of developing large clinical trials of strategies to increase cholinergic tone, either by stimulating the vagus or by increased availability of Ach, in heart failure.

Notes

Acknowledgments

The authors thank Hermona Soreq for comments on an early version of this review and Ciric To for preparation of the figure in this paper. Research by the authors is supported by the Heart & Stroke Foundation, Canadian Foundation for Innovation, Ontario Research Trust, Canadian Institutes of Health Research, The Weston Brain Institute and a multiinvestigator grant from Brain Canada (Canada). S Guatimosim was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (Brazil) and the NIH-Fogarty Center. A Roy was the recipient of an Ontario Graduate Scholarship.

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Authors and Affiliations

  • Ashbeel Roy
    • 1
    • 2
  • Silvia Guatimosim
    • 3
  • Vania F. Prado
    • 1
    • 2
    • 4
  • Robert Gros
    • 1
    • 2
    • 5
  • Marco A. M. Prado
    • 1
    • 2
    • 4
  1. 1.Robarts Research InstituteThe University of Western OntarioLondonCanada
  2. 2.Department of Physiology and PharmacologyThe University of Western OntarioLondonCanada
  3. 3.Department of Physiology and Biophysics, Institute of Biological SciencesUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  4. 4.Department of Anatomy and Cell BiologyThe University of Western OntarioLondonCanada
  5. 5.Department of MedicineUniversity of Western OntarioLondonCanada

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