Therapeutic targeting of the oncostatin M receptor-[beta] prevents inflammatory heart failure

• Published in: Basic research in cardiology Vol. 109; no. 1; p. 1
• Main 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
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.01.2014
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s00395-013-0396-3

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 (O[beta]) signaling in a mouse model of inflammatory dilative cardiomyopathy. We found that administration of an antibody directed against the extracellular domain of O[beta] or genetic inactivation of a single allele of the O[beta] gene reduced cardiomyocyte remodeling and dedifferentiation resulting in improved cardiac performance and increased survival. We conclude that pharmacological attenuation of long-lasting O[beta] signaling is a promising strategy to treat different types and stages of HF that go along with infiltration by OSM-releasing inflammatory cells.[PUBLICATION ABSTRACT]