Document Detail


Cellular FLICE-inhibitory protein protects against cardiac remodelling after myocardial infarction.
MedLine Citation:
PMID:  22202974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cellular FLICE-inhibitory protein (cFLIP) is a member of the tumour necrosis factor signalling pathway and a regulator of apoptosis, and it has a role in cardiac remodelling following myocardial infarction (MI) that remains largely uncharacterised. This study aimed to determine the function of cFLIP as a potential mediator of post-infarction cardiac remodelling. Our results show diminished cFLIP expression in failing human and murine post-infarction hearts. Genetically engineered cFLIP heterozygous (cFLIP+/-, HET) mice, cardiac-specific cFLIP-overexpressing transgenic (TG) mice and their respective wild-type (WT) and non-transgenic controls were subjected to MI by permanent ligation of their left anterior descending artery. Cardiac structure and function were assessed by echocardiography and pressure-volume loop analysis. Apoptosis, inflammation, angiogenesis, and fibrosis were evaluated in the myocardium. The HET mice showed exacerbated left ventricular (LV) contractile dysfunction, dilatation, and remodelling compared with WT mice 28 days after MI. Impaired LV function in the HET mice was associated with increases in infarct size, hypertrophy, apoptosis, inflammation, and interstitial fibrosis, and reduced capillary density. The TG mice displayed the opposite phenotype after MI. Moreover, adenovirus-mediated overexpression of cFLIP decreased LV dilatation and improved LV function and remodelling in both HET and WT mice. Further analysis of signalling events suggests that cFLIP promotes cardioprotection by interrupting JNK1/2 signalling and augmenting Akt signalling. In conclusion, our results indicate that cFLIP protects against the development of post-infarction cardiac remodelling. Thus, cFLIP gene delivery shows promise as a clinically powerful and novel therapeutic strategy for the treatment of heart failure after MI.
Authors:
Jinfeng Xiao; Mark Moon; Ling Yan; Min Nian; Yan Zhang; Chen Liu; Jing Lu; Hongjing Guan; Manyin Chen; Dingsheng Jiang; Hong Jiang; Peter P Liu; Hongliang Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-12-28
Journal Detail:
Title:  Basic research in cardiology     Volume:  107     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-28     Completed Date:  2012-04-09     Revised Date:  2012-04-25    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  239     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein / genetics,  metabolism*
Cell Proliferation
Endothelial Cells / physiology
Fibrosis
Gene Therapy
Heart Failure / metabolism*
Humans
MAP Kinase Signaling System
Mice
Mice, Knockout
Mice, Transgenic
Myocardial Infarction / immunology,  metabolism*,  mortality
Myocardium / pathology
Neovascularization, Physiologic
Proto-Oncogene Proteins c-akt / metabolism
Ventricular Remodeling*
Chemical
Reg. No./Substance:
0/CASP8 and FADD-Like Apoptosis Regulating Protein; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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