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01.09.2008 | ORIGINAL CONTRIBUTION

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

verfasst von: Stefan Frantz, MD, Kai Hu, Anna Adamek, Jürgen Wolf, Abed Sallam, Sebastian KG Maier, Scott Lonning, Hong Ling, Georg Ertl, Johann Bauersachs

Erschienen in: Basic Research in Cardiology | Ausgabe 5/2008

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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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Titel: Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction
verfasst von: Stefan Frantz, MD
Kai Hu
Anna Adamek
Jürgen Wolf
Abed Sallam
Sebastian KG Maier
Scott Lonning
Hong Ling
Georg Ertl
Johann Bauersachs
Publikationsdatum: 01.09.2008
Verlag: D. Steinkopff-Verlag
Erschienen in: Basic Research in Cardiology / Ausgabe 5/2008
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-008-0739-7

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