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Remodeling and dedifferentiation of adult cardiomyocytes during disease and regeneration

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Abstract

Cardiomyocytes continuously generate the contractile force to circulate blood through the body. Imbalances in contractile performance or energy supply cause adaptive responses of the heart resulting in adverse rearrangement of regular structures, which in turn might lead to heart failure. At the cellular level, cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus; (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism. Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is characterized by reciprocal changes in the expression pattern of “mature” and “immature” cardiomyocyte-specific genes. Dedifferentiation may enable cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding contractile machinery and by reduction of the cellular energy demand. Dedifferentiation during myocardial repair might provide cardiomyocytes with additional plasticity, enabling survival under hypoxic conditions and increasing the propensity to enter the cell cycle. Although dedifferentiation of cardiomyocytes has been described during tissue regeneration in zebrafish and newts, little is known about corresponding mechanisms and regulatory circuits in mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for cardiomyocyte dedifferentiation and exerts strong protective effects during myocardial infarction highlights the role of cytokines as potent stimulators of cardiac remodeling. Here, we summarize the current knowledge about transient dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and propose a model for the role of OSM in this process.

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Acknowledgments

The authors thank all members of the laboratory and specifically Sawa Kostin for continuous help, Jaakko Pohjoismäki (University of Eastern Finland, FIN) and Christopher Carroll (University of Helsinki, FIN) for critically reviewing this manuscript. Work in the laboratory was supported by the Max-Planck-Society, the DFG (Excellence Initiative “Cardiopulmonary System” and SFB/TRR 81), the University of Giessen-Marburg Lung Center (UGMLC) and the Cell and Gene Therapy Center (CGT) at the University of Frankfurt.

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The authors declare that they have no conflicting commercial interests related to this work.

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Authors and Affiliations

  1. Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231, Bad Nauheim, Germany

    Marten Szibor, Jochen Pöling, Thomas Kubin & Thomas Braun

  2. Research Program of Molecular Neurology, University of Helsinki, Helsinki, Finland

    Marten Szibor

  3. Department of Cardiac Surgery, Schüchtermann Clinic, Bad Rothenfelde, Germany

    Jochen Pöling & Henning Warnecke

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  1. Marten Szibor
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Correspondence to Thomas Braun.

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Szibor, M., Pöling, J., Warnecke, H. et al. Remodeling and dedifferentiation of adult cardiomyocytes during disease and regeneration. Cell. Mol. Life Sci. 71, 1907–1916 (2014). https://doi.org/10.1007/s00018-013-1535-6

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