2005 Fiscal Year Final Research Report Summary
Trial of combination therapy with anti-apoptosis and myocardial regeneration against heart failure following large myocardial infarction
| Project/Area Number |
16590669
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gifu University |
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Principal Investigator |
TAKEMURA Genzou Gifu University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (40283311)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Hisayoshi Gifu University, Graduate School of Medicine, Presser, 大学院・医学系研究科, 教授 (80115930)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Myocardial infarction / Heart failure / Myocardial regeneration / Apoptosis / Cytokine / Gene therapy |
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| Research Abstract |
We previously reported the inhibition of granulation tissue cell apoptosis during the subacute stage of myocardial infarction (MI) improved left ventricular (LV) remodeling and dysfunction at the chronic stage. It was also reported that granulocyte colony-stimulating factor (G-CSF), which can mobilize multipotent progenitor cells into the peripheral blood, improved post-MI LV remodeling and function possibly via regenerating and/or direct protective effects of myocardium. We examined here the combined effect of soluble Fas (sFas), a Fas-induced apoptosis inhibitor, and G-CSF, a regenerative cytokine, on post-MI LV remodeling and heart failure. On the 3rd day of MI, the mice were randomly assigned into 4 groups. In Group 1 (combination therapy, n=11), an adenovirus encoding sFas (Ad.sFas) was injected into the himdlimb muscles and G-CSF (100 microg/kg/day) was intraperitoneally injected for 5 days. In Group 2 (Ad.sFas alone, n=13) and in Group 3 (G-CSF alone, n=7) was similarly given. In Group 4 as a control, an adenovirus encoding LacZ gene and distilled water was injected (n=7). According to echocardiography and cardiac catheterization, Group 1 was found best in alleviating post-MI LV remodeling and dysfunction. Groups 2 and 3 were the second best. Thus, an efficacy was evident of the combined anti-apoptosis and regenerative cytokine therapies during the subacute stage of MI for LV remodeling and heart failure at the chronic stage. This novel therapeutic concept may be applied for management of patients with post-MI heart failure.
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