Skip Navigation

Cardiovascular Research 2003 57(3):749-756; doi:10.1016/S0008-6363(02)00723-X
© 2003 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Frantz, S.
Right arrow Articles by Bauersachs, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Frantz, S.
Right arrow Articles by Bauersachs, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2003, European Society of Cardiology

Sustained activation of nuclear factor kappa B and activator protein 1 in chronic heart failure

Stefan Frantza,*, Daniela Fraccarolloa, Helga Wagnera, Thomas M Behrb, Philip Jungb, Christiane E Angermannb, Georg Ertla and Johann Bauersachsa

aMedizinische Universitätsklinik Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany
bMedizinische Poliklinik der Universität Würzburg, Würzburg, Germany

* Corresponding author. Tel.: +49-931-201-36127; fax: +49-931-201-36131. s.frantz{at}mail.uni-wuerzburg.de

Objective: Innate immune response proteins such as inflammatory cytokines, inducible nitric oxide synthase, and toll like receptors are implicated in myocardial depression and left ventricular (LV) remodeling after myocardial infarction (MI). Although all these innate immunity proteins share the downstream activation of the transcription factor NF-{kappa}B (nuclear factor kappa B) and activator protein 1 (AP-1), the involvement of NF-{kappa}B and AP-1 in LV remodeling has not been demonstrated so far. Methods and results: Nuclear translocation of NF-{kappa}B and AP-1 was studied by electrophoretic mobility shift assays and ELISA 10 weeks after large experimental MI in rats, the chronic phase of LV remodeling. In the non-infarcted myocardium of MI rats, NF-{kappa}B and AP-1 were significantly activated (2.5-fold) as compared to sham-operated animals. Immunohistochemistry demonstrated NF-{kappa}B activation mainly in cardiac myocytes. Treatment with the ACE (angiotensin converting enzyme) inhibitor trandolapril led to a further 2-fold increase in the activation of NF-{kappa}B and AP-1 when compared to placebo-treated animals with the same MI size (P<0.001). Human failing hearts explanted at the time of heart transplantation exhibited marked nuclear translocation of NF-{kappa}B in cardiac myocytes when compared to control hearts. NF-{kappa}B as well as AP-1 were both significantly activated in congestive heart failure due to ischemic or dilated cardiomyopathy. Conclusion: In experimental and human heart failure, both NF-{kappa}B and AP-1 are chronically activated in cardiac myocytes. These findings suggest an important involvement of NF-{kappa}B and AP-1 in the cardiac remodeling process.

KEYWORDS Cytokines; Immunology; Infarction; Remodeling


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.