Therapeutic targeting of the oncostatin M receptor-β …10.1007...Therapeutic targeting of the...

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1 Supplementary Materials Therapeutic targeting of the oncostatin M receptor-β prevents inflammatory heart failure Jochen Pöling 1,2* ; Praveen Gajawada 1* , Manfred Richter 3 , Holger Lörchner 1 , Silvia Schimanski 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# and Thomas Braun 1# 1 Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, Bad Nauheim, 61321, Germany 2 Department of Cardiac Surgery, Schüchtermann-Clinic, Ulmenallee 5, Bad Rothenfelde, 49214, Germany 3 Department of Cardiac Surgery, Kerckhoff Hospital, Benekestrasse 2-8, Bad Nauheim, 61231, Gerrmany 4 University of Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58448, Germany

Transcript of Therapeutic targeting of the oncostatin M receptor-β …10.1007...Therapeutic targeting of the...

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Supplementary Materials

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

Jochen Pöling1,2*; Praveen Gajawada1*, Manfred Richter3, Holger Lörchner1, Silvia

Schimanski1, Victoria Polyakova1,3, Sawa Kostin1, Jaeyoung Shin1, Thomas Boettger1,

Thomas Walther3, Wolfgang Rees2; Astrid Wietelmann1, Henning Warnecke2,4, Thomas

Kubin1# and Thomas Braun1#

1 Department of Cardiac Development and Remodelling, Max Planck Institute

for Heart and Lung Research, Ludwigstrasse 43, Bad Nauheim, 61321, Germany

2 Department of Cardiac Surgery, Schüchtermann-Clinic, Ulmenallee 5,

Bad Rothenfelde, 49214, Germany

3 Department of Cardiac Surgery, Kerckhoff Hospital, Benekestrasse 2-8,

Bad Nauheim, 61231, Gerrmany

4 University of Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58448, Germany

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Suppl. Fig. S1: Increased Oβ/gp130 signaling but unstable activation of Erk1/2 during

early stages of DCM in MCP-1 mice. (A) Western blot analysis of Oβ/gp130 and Erk1/2

signaling in wild-type and MCP-1 transgenic mouse hearts at 2 to 4 weeks after birth (n=4 per

time point). (B) Western blot analysis of Oβ/gp130 and Erk1/2 signaling in 2 months old wild

type and MCP-1 mouse hearts. No significant increase of Erk1/2 phosphorylation is

detectable at this age despite increased Oβ/gp130 signaling (n=4). (C) Western blot analysis

of increased Erk1/2 phosphorylation in 6 months old MCP-1 but not wild type hearts (n=5 for

each group). (D) Inhibition of Oβ signaling by antibodies against Oβ or removal of a single

allele of Oβ leads to decreased Erk1/2 phosphorylation in 6 month old MCP-1 mice (n=5 for

each group).

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Suppl. Fig. S2: Reduced apoptosis of cardiomyocytes in 6 months old MCP-1 mice after

treatment with antibodies against Oβ or removal of a single allele of Oβ. Confocal

immunofluorescence analysis of hearts from wild type, MCP-1, anti-Oβ antibody treated

MCP-1 and MCP-1/Oβ(+/-) mice after TUNEL-staining. Cardiomyocytes are identified by

staining with antibodies against sarcomeric actinin (green). A statistical analysis is shown

(n=3 for each group).

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Supplementary Movie S1. MRI Analysis of Heart Functions: (A) Cine MRI analysis of the

heart function of MCP-1 transgenic mice at the age of 4 months before treatment with a

isotype matched control antibody or with anti-Oβ antibody. (B) Cine MRI analysis of the

heart function of MCP-1 transgenic mice at the age of 6 months after treatment with a control

antibody or with anti-Oβ antibody. Please note improved heart function of MCP-1 mice

treated with anti-Oβ antibody.