TY  - JOUR
A1  - Pachel, Christina
A1  - Mathes, Denise
A1  - Bayer, Barbara
A1  - Dienesch, Charlotte
A1  - Wangorsch, Gaby
A1  - Heitzmann, Wolfram
A1  - Lang, Isabell
A1  - Ardehali, Hossein
A1  - Ertl, Georg
A1  - Dandekar, Thomas
A1  - Wajant, Harald
A1  - Frantz, Stefan
T1  - Exogenous Administration of a Recombinant Variant of TWEAK Impairs Healing after Myocardial Infarction by Aggravation of Inflammation
T2  - PLoS ONE
N2  - Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factorinducible 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.
KW  - apoptosis
KW  - myocardial infarction
KW  - neutrophils
KW  - cytokines
KW  - inflammation
KW  - myocardium
KW  - heart
KW  - extracellular matrix
Y1  - 2013
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/12988
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-129889
VL  - 8
IS  - 11
ER  -