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Basic Research in Cardiology

, 109:396 | Cite as

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

  • Jochen Pöling
  • Praveen Gajawada
  • Manfred Richter
  • Holger Lörchner
  • Victoria Polyakova
  • Sawa Kostin
  • Jaeyoung Shin
  • Thomas Boettger
  • Thomas Walther
  • Wolfgang Rees
  • Astrid Wietelmann
  • Henning Warnecke
  • Thomas KubinEmail author
  • Thomas BraunEmail author
Original Contribution

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.

Keywords

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

Notes

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.

Supplementary material

395_2013_396_MOESM1_ESM.pdf (3.6 mb)
Supplementary material 1 (PDF 3637 kb)

Supplementary material 2 (MPG 9494 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jochen Pöling
    • 1
    • 2
  • Praveen Gajawada
    • 1
  • Manfred Richter
    • 3
  • Holger Lörchner
    • 1
  • Victoria Polyakova
    • 1
    • 3
  • Sawa Kostin
    • 1
  • Jaeyoung Shin
    • 1
  • Thomas Boettger
    • 1
  • Thomas Walther
    • 3
  • Wolfgang Rees
    • 2
  • Astrid Wietelmann
    • 1
  • Henning Warnecke
    • 2
    • 4
  • Thomas Kubin
    • 1
    Email author
  • Thomas Braun
    • 1
    Email author
  1. 1.Department of Cardiac Development and RemodellingMax-Planck-Institute for Heart and Lung ResearchBad NauheimGermany
  2. 2.Department of Cardiac SurgerySchüchtermann-KlinikBad RothenfeldeGermany
  3. 3.Department of Cardiac SurgeryKerckhoff-KlinikBad NauheimGermany
  4. 4.University of Witten/HerdeckeWittenGermany

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