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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129889
VL  - 8
IS  - 11
ER  - 
TY  - THES
A1  - Wangorsch, Gaby
T1  - Mathematical modeling of cellular signal transduction
T1  - Mathematische Modellierung der zellulären Signaltransduktion
N2  - A subtly regulated and controlled course of cellular processes is essential for the healthy functioning not only of single cells, but also of organs being constituted thereof. In return, this entails the proper functioning of the whole organism. This implies a complex intra- and inter-cellular communication and signal processing that require equally multi-faceted methods to describe and investigate the underlying processes. Within the scope of this thesis, mathematical modeling of cellular signaling finds its application in the analysis of cellular processes and signaling cascades in different organisms. ...
N2  - Das fein regulierte und kontrollierte Ablaufen zellulärer Prozesse ist essentiell für das gesunde Funktionieren einzelner Zellen, sowie der aus ihnen bestehenden Organe. Diese wiederum bedingen das Funktionieren des gesamten Organismus. Genauso vielschichtig wie die Kommunikation und Signalverarbeitung innerhalb und zwischen den Zellen, sind die Methoden um diese Vorgänge zu beschreiben und zu untersuchen. Die mathematische Modellierung zellulärer Signalverarbeitung findet im Rahmen dieser Arbeit Anwendung in der Analyse zellulärer Prozesse und Signalkaskaden in verschiedenen Organismen....
KW  - Mathematische Modellierung
KW  - Thrombozyt
KW  - Systembiologie
KW  - Mathematische Modellierung
KW  - Mathematical modeling
KW  - platelets
KW  - signaling pathway
KW  - systems biology
KW  - Signaltransduktion
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87746
ER  -