2005 Fiscal Year Final Research Report Summary
Non-invasive regeneration therapy of dilated cardiomyopathy using G-CSF
| Project/Area Number |
15209027
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 |
FUJIWARA Hisayoshi Gifu University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80115930)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEMURA Genzou Gifu University, University Hospital, Lecturer, 医学部附属病院, 講師 (40283311)
ARAI Masazumi Gifu University, University Hospital, Lecturer, 医学部附属病院, 講師 (00202721)
KOSAI Kenichirou Kurume University, Cognitive and Molecular Research Institute of Brain Diseases, Professor, 高次脳疾患研究所, 教授 (90258418)
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| Project Period (FY) |
2003 – 2005
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| Keywords | dilated cardiomyopathy / cytokine / autophagy / G-CSF / heart failure / remodeling / apotosis / cardiomyocyte regeneration |
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| Research Abstract |
In UM-X7.1 strain hamsters, a model of human dilated cardiomyopathy, heart failure progressively develops and a half of them die by 30 weeks old. We ultrastructurally found typical autophagic vacuoles including degraded mitochondria, glycogen granules, and myelin-like figures and overexpressed ubiquitin, cathepsin D and Rab7 in many cardiomyocytes of this model. Importantly, most cardiomyocytes with leaky plasma membrane were positive for cathepsin D, suggesting a direct linkage between autophagic degeneration and cell death. Meanwhile, cardiomyocyte apoptosis appeared insignificant. Injection of granulocyte colony-stimulating factor (10 μg/kg/day) 5 days/week for 15 weeks, started at 15 weeks of age, improved survival among 30-week-old hamsters (100% vs. 53% in the untreated hamsters, p<0.0001), ventricular function and remodeling, increased cardiomyocyte size, and reduced myocardial fibrosis, followed by a dramatic reduction in the autophagic findings. It also resulted in downregulation of tumor necrosis factor-α and increase in activities of Akt, signal transducer and activator of transcription-3, and matrix metalloproteinases. However, there was no clear evidence of transdifferentiation from bone marrow cells into cardiomyocytes. In conclusion, autophagic death is important for cardiomyocyte loss in the cardiomyopathic hamster and granulocyte colony-stimulating factor has the beneficial effect mainly via antiautophagic mechanism rather than antiapoptosis or regeneration.
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[Journal Article] Autophagic cardiomyocyte death in cardiomyopathic hamsters and its prevention by granulocyte colony-stimulating factor.2006
Author(s)
Miyata S, Takemura G, Kawase Y, Li Y, Okada H, Maruyama R, Ushikoshi H, Kanamori H, Li L, Misao Y, Tezuka A, Toyo-oka T, Minatoguchi S, Fujiwara T, Fujiwara H
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Journal Title
Am J Pathol 168(2)
Pages: 386-397
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Postinfarction Gene Therapy Against Transforming Growth Factor-β Signal Modulates Infarct Tissue Dynamics and Attenuates Left Ventricular Remodeling and Heart Failure.2005
Author(s)
Okada H, Takemura G, Kosai K, Li Y, Takahashi T, Esaki M, Yuge K, Miyata S, Maruyama R, Mikami A, Minatoguchi S, Fujiwara T, Fujiwara H
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Journal Title
Circulation 111(19)
Pages: 2430-2437
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment.2004
Author(s)
Minatoguchi S, Takemura G, Chen X, Wang N, Uno Y, Koda M, Arai M, Misao Y, Lu C, Suzuki K, Goto K, Komada A, Takahashi T, Kosai K, Fujiwara T, Fujiwara H
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Journal Title
Circulation 109(21)
Pages: 2572-2580
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Critical roles for the fas/fas ligand system in postinfarction ventricular remodeling and heart failure.2004
Author(s)
Li Y, Takemura G, Kosai K, Takahashi T, Okada H, Miyata S, Yuge K, Nagano S, Esaki M, N.C.Khai, Goto K, Mikami A, Maruyama R, Minatoguchi S, Fujiwara T, Fujiwara H
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Journal Title
Circ Res 95(6)
Pages: 627-636
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Postinfarction treatment with an adenoviral vector expressing hepatocyte growth factor relieves chronic left ventricular remodeling and dysfunction in mice.2003
Author(s)
Li Y, Takemura G, Kosai K, Yuge K, Nagano S, Esaki M, Goto K, Takahashi T, Hayakawa K, Koda M, Kawase Y, Maruyama R, Okada H, Minatoguchi S, Mizuguchi H, Fujiwara T, Fujiwara H
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Journal Title
Circulation 107(19)
Pages: 2499-2506
Description
「研究成果報告書概要(欧文)」より
