Critical roles for the Fas/Fas ligand system in postinfarction ventricular remodeling and heart failure
Autor: | Ken-ichiro Kosai, Tomoyuki Takahashi, Yiwen Li, Kentaro Yuge, Ngin Cin Khai, Shusaku Miyata, Rumi Maruyama, Satoshi Nagano, Takako Fujiwara, Atsushi Mikami, Hisayoshi Fujiwara, Masayasu Esaki, Shinya Minatoguchi, Kazuko Goto, Hideshi Okada, Genzou Takemura |
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Rok vydání: | 2004 |
Předmět: |
Male
Fas Ligand Protein Time Factors Physiology Genetic enhancement Genetic Vectors Myocardial Infarction Apoptosis Gene delivery Fas ligand Adenoviridae Cicatrix Mice Genes Synthetic Medicine Animals Humans fas Receptor Ventricular remodeling Ligation Heart Failure Membrane Glycoproteins Ventricular Remodeling business.industry Myocardium Granulation tissue Defective Viruses Transfection Genetic Therapy medicine.disease Coronary Vessels Mice Mutant Strains Mice Inbred C57BL medicine.anatomical_structure Solubility Heart failure Caspases Immunoglobulin G Immunology Cancer research Granulation Tissue Hypertrophy Left Ventricular Cardiology and Cardiovascular Medicine business |
Zdroj: | Circulation research. 95(6) |
ISSN: | 1524-4571 |
Popis: | 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. |
Databáze: | OpenAIRE |
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