Skip Navigation

Cardiovascular Research 2000 48(1):101-110; doi:10.1016/S0008-6363(00)00154-1
© 2000 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 Imanishi, T.
Right arrow Articles by Han, D. K.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Imanishi, T.
Right arrow Articles by Han, D. K.M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2000, European Society of Cardiology

Cellular FLIP is expressed in cardiomyocytes and down-regulated in TUNEL-positive grafted cardiac tissues

Toshio Imanishia,*, Charles E. Murryb, Hans Reineckeb, Takuzo Hanoa, Ichiro Nishioa, W.Conrad Lilesc, Leonard Hofstaf, Koanhoi Kimb, Kevin D. O'Briend, Stephen M. Schwartzb and David K.M. Hane

aDivision of Cardiology, Department of Medicine, Wakayama Medical College, 811-1, Kimiidera, Wakayama City, Wakayama 641-8510, Japan
bDepartment of Pathology, University of Washington, Seattle, WA, USA
cDepartment of Medicine (Infectious Diseases), University of Washington, Seattle, WA, USA
dDepartment of Medicine (Cardiology), University of Washington, Seattle, WA, USA
eDepartment of Molecular Biotechnology, University of Washington, Seattle, WA, USA
fDepartment of Cardiology, University of Maastricht, Masstricht, The Netherlands

* Corresponding author. Tel.: +81-73-441-0621; fax: +81-73-446-0631 imanishi{at}wakayama.hosp.go.jp

Objective: c-FLIP is a natural homologue of caspase 8, and may antagonize activation of death pathways mediated by FADD. c-FLIP is highly expressed in the heart, and a recent report suggests that c-FLIP may protect against certain types of myocyte death. The present study was designed to define the expression patterns of c-FLIP in the heart. Methods: The expression pattern of c-FLIP in end-stage human hearts, and rat cardiomyocyte grafting models was analyzed by in situ hybridization, immunohistochemistry and TUNEL assay. In addition, to determine whether Fas-dependent pathway is active in cardiomyocytes in vitro, we examined whether activated monocytes can kill neonatal cardiomyocytes in a co-culture system. Results: c-FLIP mRNA and protein were abundantly expressed in normal cardiomyocytes from failing human heart. In animal models, c-FLIP protein was absent in TUNEL-positive grafted cardiomyocytes. Double staining demonstrated that c-FLIP-positive cells rarely had fragmented DNA, while TUNEL-positive cells rarely contained c-FLIP. Finally, activated monocytes induced death of neonatal rat cardiomyocytes via the Fas/FasL system. Conclusions: Loss of c-FLIP expression correlates with cardiomyocyte cell death. We hypothesize that diminished c-FLIP expression may predispose cardiomyocytes to apoptotic death.

KEYWORDS Apoptosis; Cardiomyopathy; Heart failure; Histo(patho)logy; Myocytes


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.