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Therapeutic targeting of the oncostatin M receptor-β prevents inflammatory heart failure

Abstract

Heart failure (HF) is a common and potentially deadly condition, which frequently develops as a consequence of various diseases of the heart. The incidence of heart failure continuously increases in aging societies illustrating the need for new therapeutic approaches. We recently discovered that continuous activation of oncostatin M (OSM), a cytokine of the interleukin-6 family that induces dedifferentiation of cardiomyocytes, promotes progression of heart failure in dilative cardiomyopathy. To evaluate whether inhibition of OSM signaling represents a meaningful therapeutic approach to prevent heart failure we attenuated OSM-receptor (Oβ) signaling in a mouse model of inflammatory dilative cardiomyopathy. We found that administration of an antibody directed against the extracellular domain of Oβ or genetic inactivation of a single allele of the Oβ gene reduced cardiomyocyte remodeling and dedifferentiation resulting in improved cardiac performance and increased survival. We conclude that pharmacological attenuation of long-lasting Oβ signaling is a promising strategy to treat different types and stages of HF that go along with infiltration by OSM-releasing inflammatory cells.

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Acknowledgments

The authors thank Jutta Wetzel, Kerstin Richter, Brigitte Matzke and Marion Wiesnet for excellent technical assistance. This work was supported by the Max-Planck-Society, the Excellence Cluster Cardiopulmonary System (ECCPS), the University of Giessen-Marburg Lung Center (UGMLC), and the German Center for Cardiovascular Research (DZHK). The authors declare that they have no conflicting commercial interests related to this work.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Author information

Correspondence to Thomas Kubin or Thomas Braun.

Additional information

J. Pöling and P. Gajawada contributed equally.

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Pöling, J., Gajawada, P., Richter, M. et al. Therapeutic targeting of the oncostatin M receptor-β prevents inflammatory heart failure. Basic Res Cardiol 109, 396 (2014). https://doi.org/10.1007/s00395-013-0396-3

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Keywords

  • Dedifferentiation
  • Dilative cardiomyopathy
  • Cytokine
  • Cell survival program
  • Myoglobin
  • Insulin growth factor-1 (IGF-1)