Exogenous administration of a recombinant variant of TWEAK impairs healing after myocardial infarction by aggravation of inflammation

Christina Pachel, Denise Mathes, Barbara Bayer, Charlotte Dienesch, Gaby Wangorsch, Wolfram Heitzmann, Isabell Lang, Hossein Ardehali, Georg Ertl, Thomas Dandekar, Harald Wajant, Stefan Frantz

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are upregulated after myocardial infarction (MI) in both humans and mice. They modulate inflammation and the extracellular matrix, and could therefore be important for healing and remodeling after MI. However, the function of TWEAK after MI remains poorly defined. Methods and results: Following ligation of the left coronary artery, mice were injected twice per week with a recombinant human serum albumin conjugated variant of TWEAK (HSA-Flag-TWEAK), mimicking the activity of soluble TWEAK. Treatment with HSA-Flag-TWEAK resulted in significantly increased mortality in comparison to the placebo group due to myocardial rupture. Infarct size, extracellular matrix remodeling, and apoptosis rates were not different after MI. However, HSA-Flag-TWEAK treatment increased infiltration of proinflammatory cells into the myocardium. Accordingly, depletion of neutrophils prevented cardiac ruptures without modulating all-cause mortality. Conclusion: Treatment of mice with HSA-Flag-TWEAK induces myocardial healing defects after experimental MI. This is mediated by an exaggerated neutrophil infiltration into the myocardium.

Original languageEnglish (US)
Article numbere78938
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 11 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Pachel, C., Mathes, D., Bayer, B., Dienesch, C., Wangorsch, G., Heitzmann, W., Lang, I., Ardehali, H., Ertl, G., Dandekar, T., Wajant, H., & Frantz, S. (2013). Exogenous administration of a recombinant variant of TWEAK impairs healing after myocardial infarction by aggravation of inflammation. PloS one, 8(11), [e78938]. https://doi.org/10.1371/journal.pone.0078938