2004 Fiscal Year Final Research Report Summary
NEW TREATMENT FOR PULMONAY HYPERTENSION
| Project/Area Number |
14370234
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | KURUME UNIVERSITY |
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Principal Investigator |
IMAIZUMI Tsutomu Kurume University, School of Medicine, Professor, 医学部, 教授 (60148947)
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| Co-Investigator(Kenkyū-buntansha) |
KAI Hisashi Kurume University, School Of Medicine, Associate Professor, 医学部, 助教授 (60281531)
MUROHARA Toyoaki Nagoya University, School Of Medicine, Professor, 医学部, 教授 (90299503)
TAHARA Nobuhiro Kurume University, School Of Medicine, Assistant Professor, 医学部, 助手 (10320186)
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| Project Period (FY) |
2002 – 2004
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| Keywords | pulmonary hypertension / prostacyclin / gene therapy / stem cel / cell transplantation / macrophages |
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| Research Abstract |
(1)Naked plasmid encoding the prostacyclin synthase (PGIS) gene was injected into the thigh muscle every 7 days from 1 week and 4weeks after monocrotaline injection in rats. PGIS gene transfer increased intramuscular and serum 6-keto-prostaglandin F2-alpha, a stable metabolite of prostacyclin. Repeated PGIS gene transfers significantly reduced pulmonary arterial pressure and ameliorated right ventricular hypertrophy and pulmonary arterial remodeling in monocrotaline-treated rats. Furthermore, survival rate was significantly improved by repeated PGIS gene transfers.
(2)In normal rats, 3% of intravenously implanted bone marrow-derived mononuclear cells (BM-MNCs) accumulated in the lung 1 day after cell transplantation. Two weeks after cell transplantation, only 1 % of tranplnted BM-MNCs were detected in the lung. In contrast, the rate of lung distribution of transplanted BM-MNCs were remarkably increased in monocrotalin-induced pulmonary hypertension rats (10% and 6% at days 1 and 14, respectively).
(3)We established BM-MNC line, which overexpresses PGIS gene and produces prostacyclin, by using a retroviral vector-mediated gene transfer of PGIS.
(4)Transplantation of PGIS-overexpressing BM-MNCs significantly reduced pulmonary arterial pressure and ameliorated right ventricular hypertrophy in monocrotaline-induced pulmonary hypertension rats.
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[Journal Article] Advanced glycation end products activate mesangial TGF-β-Smad signaling via angiotensin II-type I receptor interaction.2004
Author(s)
Fukami K, Ueda S, Yamagishi S, Kato S, Inagaki Y, Takeuchi M, Motoyama Y, Bucala R, Iida S, Tamaki K, Imaizumi T, Cooper EM, Okuda S
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Journal Title
Kidny Int 66
Pages: 2137-2147
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Repeated gene transfer of naked prostacyclin synthase plasmid into skeletal muscle attenuates monocrotaline -induced pulmonary hypertension and prolongs survival in rats.2004
Author(s)
Tahara N, Kai H, Niiyama H, Mori T, Sugi Y, Takayama N, Yasukawa H, Numaguchi Y, Matsui H, Okumura K, Imaizumi T
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Journal Title
Human Gene Ther 15
Pages: 1270-1278
Description
「研究成果報告書概要(欧文)」より
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