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  - JOUR
A1  - Benz, Peter M.
A1  - Merkel, Carla J.
A1  - Offner, Kristin
A1  - Abeßer, Marco
A1  - Ullrich, Melanie
A1  - Fischer, Tobias
A1  - Bayer, Barbara
A1  - Wagner, Helga
A1  - Gambaryan, Stepan
A1  - Ursitti, Jeanine A.
A1  - Adham, Ibrahim M.
A1  - Linke, Wolfgang A.
A1  - Feller, Stephan M.
A1  - Fleming, Ingrid
A1  - Renné, Thomas
A1  - Frantz, Stefan
A1  - Unger, Andreas
A1  - Schuh, Kai
T1  - Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy
JF  - Cell Communication and Signaling
N2  - Background: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks.
Results: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired.
Conclusions: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.
KW  - Mena/VASP
KW  - dilated cardiomyopathy
KW  - actin
KW  - heart
KW  - spectrin
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128760
VL  - 11
IS  - 56
ER  -