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Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction

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Abstract

Background

Transforming growth factor (TGF)-β is a locally generated cytokine involved in healing processes and tissue fibrosis, all relevant for cardiac remodeling and the development of heart failure after myocardial infarction (MI). However, data regarding the function of TGF-β after ischemic injury are inconclusive.

Methods and results

We tested the effect of TGF-β inhibition by application of a blocking antibody in mice with MI. Starting 1 week before or 5 days after coronary artery ligation mice were treated with intraperitoneal injections of an anti-TGF-β (5 mg/kg bodyweight 1D11, Genzyme) or control antibody. Mortality over 8 weeks was significantly higher in the groups treated with the anti-TGF-β antibody. Both, pre or post MI treatments were associated with increased left ventricular dilatation after MI as determined by serial echocardiography. In anti-TGF-β treated mice collagen production decreased and matrix-metalloproteinase expression increased. However, the expression of TGF pro-inflammatory cytokine TNF-α was not altered by the treatment.

Summary

Anti-TGF-β treatment before or after coronary artery ligation increases mortality and worsens left ventricular remodeling in mice with non-reperfused MI. The detrimental effects of TGF-β inhibition may be mediated by alterations in extracellular matrix remodeling.

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Acknowledgments

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 688, TP A10) and by Genyzme Corporation, Framingham, MA, USA.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, Herz-/Kreislaufzentrum, Universitätsklinikum Würzburg, Josef Schneider-Straße 2, 97080, Würzburg, Germany

    Stefan Frantz MD, Kai Hu, Anna Adamek, Jürgen Wolf, Abed Sallam, Sebastian KG Maier, Georg Ertl & Johann Bauersachs

  2. Genzyme Corporation, Framingham, MA, USA

    Scott Lonning & Hong Ling

Authors
  1. Stefan Frantz MD
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  2. Kai Hu
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  3. Anna Adamek
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  9. Georg Ertl
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Corresponding author

Correspondence to Stefan Frantz MD.

Additional information

Returned for 1. Revision: 2 January 2008 1. Revision received: 18 April 2008

Returned for 2. Revision: 14 May 2008 2. Revision received: 19 May 2008

Returned for 3. Revision: 19 June 2008 3. Revision received: 24 June 2008

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Frantz, S., Hu, K., Adamek, A. et al. Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Res Cardiol 103, 485–492 (2008). https://doi.org/10.1007/s00395-008-0739-7

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  • DOI: https://doi.org/10.1007/s00395-008-0739-7

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