Document Detail


Critical roles for the Fas/Fas ligand system in postinfarction ventricular remodeling and heart failure.
MedLine Citation:
PMID:  15297380     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In myocardial infarction (MI), granulation tissue cells disappear via apoptosis to complete a final scarring with scanty cells. Blockade of this apoptosis was reported to improve post-MI ventricular remodeling and heart failure. However, the molecular biological mechanisms for the apoptosis are unknown. Fas and Fas ligand were overexpressed in the granulation tissue at the subacute stage of MI (1 week after MI) in mice, where apoptosis frequently occurred. In mice lacking functioning Fas (lpr strain) and in those lacking Fas ligand (gld strain), apoptotic rate of granulation tissue cells was significantly fewer compared with that of genetically controlled mice, and post-MI ventricular remodeling and dysfunction were greatly attenuated. Mice were transfected with adenovirus encoding soluble Fas (sFas), a competitive inhibitor of Fas ligand, on the third day of MI. The treatment resulted in suppression of granulation tissue cell apoptosis and produced a thick, cell-rich infarct scar containing rich vessels and bundles of smooth muscle cells with a contractile phenotype at the chronic stage (4 weeks after MI). This accompanied not only alleviation of heart failure but also survival improvement. However, the sFas gene delivery during scar tissue phase was ineffective, suggesting that beneficial effects of the sFas gene therapy owes to inhibition of granulation tissue cell apoptosis. The Fas/Fas ligand interaction plays a critical role for granulation tissue cell apoptosis after MI. Blockade of this apoptosis by interfering with the Fas/Fas ligand interaction may become one of the therapeutic strategies against chronic heart failure after large MI.
Authors:
Yiwen Li; Genzou Takemura; Ken-ichiro Kosai; Tomoyuki Takahashi; Hideshi Okada; Shusaku Miyata; Kentaro Yuge; Satoshi Nagano; Masayasu Esaki; Ngin Cin Khai; Kazuko Goto; Atsushi Mikami; Rumi Maruyama; Shinya Minatoguchi; Takako Fujiwara; Hisayoshi Fujiwara
Publication Detail:
Type:  Journal Article     Date:  2004-08-05
Journal Detail:
Title:  Circulation research     Volume:  95     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-17     Completed Date:  2005-04-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  627-36     Citation Subset:  IM    
Affiliation:
Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Antigens, CD95 / genetics,  physiology*,  therapeutic use
Apoptosis / physiology*
Caspases / analysis
Cicatrix / pathology
Coronary Vessels
Defective Viruses / genetics
Fas Ligand Protein
Gene Therapy
Genes, Synthetic
Genetic Vectors / therapeutic use
Granulation Tissue / pathology*
Heart Failure / etiology,  physiopathology*,  prevention & control
Humans
Hypertrophy, Left Ventricular / etiology,  physiopathology,  prevention & control
Immunoglobulin G / genetics
Ligation
Male
Membrane Glycoproteins / deficiency,  genetics,  physiology*
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Myocardial Infarction / complications,  physiopathology*,  therapy
Myocardium / pathology*
Solubility
Time Factors
Ventricular Remodeling / physiology*
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Immunoglobulin G; 0/Membrane Glycoproteins; EC 3.4.22.-/Caspases
Comments/Corrections
Comment In:
Circ Res. 2004 Sep 17;95(6):554-6   [PMID:  15375021 ]

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


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