Fischer, Andrea, Bockstahler, Mariella, Mueller, Anna-Maria, Stroikova, Vera, Leib, Christoph, Pfitzer, Gabriele, Katus, Hugo A. and Kaya, Ziya (2019). FN14 Signaling Plays a Pathogenic Role in a Mouse Model of Experimental Autoimmune Myocarditis. J. Card. Fail., 25 (8). S. 674 - 686. PHILADELPHIA: CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. ISSN 1532-8414

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Abstract

Background: The pathogenesis of inflammatory cardiomyopathy is affected by the activation of autoimmune-mediated cascades. To study these cascades, we developed an experimental model of troponin I (TnI)-induced autoimmune myocarditis (EAM). One factor playing a pivotal role in the context of auto immune disorders is the receptor fibroblast growth factor-inducible 14 (FN14). Thus, the impact of FN14 in the development of autoimmune myocarditis was investigated. Methods and Results: TnI-immunization led to a significantly increased myocardial FN14 mRNA and protein expression in wild-type (wt) mice. To investigate the precise role of FN14 in EAM, FN14 knockout (ko) and wt littermates were immunized with TnI or control buffer. The animals were evaluated for cardiac parameters and indicators of myocardial injury. FN14 deficiency resulted in better cardiac performance, less myocardial inflammation, fibrosis, and cardiac damage. A lower myocardial mRNA expression of inflammatory cytokines and chemokines as well as their receptors could be demonstrated in TnI-immunized FN14ko compared to wt mice also immunized with TnI. Western blot analysis revealed a contribution of nuclear factor kappa-light-chain-enhancer of activated B cells to FN14-induced signaling cascades. Conclusions: In the pathogenesis of autoimmune myocarditis, the inflammatory response to cardiac injury is attenuated in FN14ko mice. Thus, inhibition of FN14 in patients might represent a novel therapeutic strategy in the treatment of inflammatory cardiomyopathy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fischer, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bockstahler, MariellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Anna-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroikova, VeraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leib, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfitzer, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Katus, Hugo A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaya, ZiyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-145378
DOI: 10.1016/j.cardfail.2019.06.003
Journal or Publication Title: J. Card. Fail.
Volume: 25
Number: 8
Page Range: S. 674 - 686
Date: 2019
Publisher: CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
Place of Publication: PHILADELPHIA
ISSN: 1532-8414
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MATRIX METALLOPROTEINASES; TWEAK/FN14 PATHWAY; GENE-EXPRESSION; APOPTOSIS TWEAK; WEAK INDUCER; CYTOKINE; PROMOTES; DEFICIENCY; ACTIVATION; PRESERVESMultiple languages
Cardiac & Cardiovascular SystemsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14537

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