title: 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.
authors.affiliation: Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61321, Bad Nauheim, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Pöling
authors.forename: Praveen
authors.initials: P
authors.lastname: Gajawada
authors.forename: Manfred
authors.initials: M
authors.lastname: Richter
authors.forename: Holger
authors.initials: H
authors.lastname: Lörchner
authors.forename: Victoria
authors.initials: V
authors.lastname: Polyakova
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.forename: Jaeyoung
authors.initials: J
authors.lastname: Shin
authors.forename: Thomas
authors.initials: T
authors.lastname: Boettger
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rees
authors.forename: Astrid
authors.initials: A
authors.lastname: Wietelmann
authors.forename: Henning
authors.initials: H
authors.lastname: Warnecke
authors.forename: Thomas
authors.initials: T
authors.lastname: Kubin
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D054337:Cell Dedifferentiation; D004195:Disease Models, Animal; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007334:Insulin-Like Growth Factor I; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D053681:Oncostatin M Receptor beta Subunit / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D057134:Antibodies, Neutralizing; D053681:Oncostatin M Receptor beta Subunit; D007334:Insulin-Like Growth Factor I