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Cell-Cycle Signaling, Epigenetics, and Nuclear Function

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Signaling in the Heart

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Abstract

Like many other cells, mammalian cardiac cells are able to divide and proliferate during development and during a short time after birth. However, the ability to divide decreases dramatically in the neonatal period, and adult cardiomyocytes are unable to proliferate. In contrast, postnatal cardiomyocytes from some lower vertebrates (e.g., zebrafish, newt) maintain the capability to divide, although the mechanisms underlying these species differences are unknown.

As a result of the inability of adult cardiac cells to proliferate, the heart is unable to regenerate new functional tissue following injury, which can cause myocardium dysfunction and even death. Recently, the dogma that the heart is a terminally differentiated nonproliferating organ has been challenged as cardiac stem cells capable of converting to cardiomyocyte-like cells were identified. Thus, in the last several years, two strategies have been used for cardiac repair: induction of endogenous cardiomyocyte proliferation and cell replacement therapy.

Our understanding of the mechanisms that control proliferation of cardiovascular cells has increased significantly in recent years. Studies in proliferating cells and animal models have identified groups of genes and proteins that control cell division; cyclins, cyclin-dependent kinases, and their inhibitors are essential for cell cycle progression, and the retinoblastoma protein and transcription factors (i.e., E2F) modulate the activities of cell cycle-regulators.

In this chapter, we review the cell cycle machinery and discuss how this controls the proliferation of cardiomyocytes. In addition, we analyze the role of sirtuin-depended deacylation in cell cycle progression and proliferation, the functioning and regulation of telomere/telomerase system, and the integration of reactive oxygen species into cell proliferation. New insights into the epigenetic components of cell inheritance, the stable transmission of cellular information beyond just DNA, highlighting DNA methylation, and chromatin organization as major candidates for carriers of epigenetic information are also presented.

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Authors and Affiliations

  1. The Molecular Cardiology and Neuromuscular Institute, Raritan Avenue 75, 08904, Highland Park, NJ, USA

    José Marín-García M.D. (Director)

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  1. José Marín-García M.D.
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Correspondence to José Marín-García M.D. .

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Marín-García, J. (2011). Cell-Cycle Signaling, Epigenetics, and Nuclear Function. In: Signaling in the Heart. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9461-5_2

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  • DOI: https://doi.org/10.1007/978-1-4419-9461-5_2

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