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- Title
Therapeutic targeting of the oncostatin M receptor-β prevents inflammatory heart failure.
- Authors
Pöling, Jochen; Gajawada, Praveen; Richter, Manfred; Lörchner, Holger; Polyakova, Victoria; Kostin, Sawa; Shin, Jaeyoung; Boettger, Thomas; Walther, Thomas; Rees, Wolfgang; Wietelmann, Astrid; Warnecke, Henning; Kubin, Thomas; Braun, Thomas
- 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.
- Subjects
TARGETED drug delivery; ONCOSTATIN M; HEART failure; INFLAMMATION; HEART cells; INTERLEUKIN-6; PREVENTION
- Publication
Basic Research in Cardiology, 2014, Vol 109, Issue 1, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-013-0396-3