PREVENTION OF VASCULAR REMODELING BY INHIBITING EARLY INFLAMMATORY PROCESS - GENE THERAPY USING A MUTANT INTERFERON-GAMMA RECEPTOR GENE -
| Project/Area Number |
13670769
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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 | KURUME UNIVERSITY |
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Principal Investigator |
SEKI Yukihiko Kurume University School of Medicine ・ Assistant Professor, 医学部, 助手 (00279168)
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| Co-Investigator(Kenkyū-buntansha) |
NIIYAMA Hiroshi Kurume University School of Medicine ・ Assistant Professor, 医学部, 助手 (30309778)
KUWAHARA Fumitaka Kurume University School of Medicine ・ Assistant Professor, 医学部, 助手 (90279167)
KAI Hisashi Kurume University ・ Cardiovascular Research Institute ・ Associate professor, 循環器病研究所, 助教授 (60281531)
AKASHI Hidetoshi Kurume University School of Medicine ・ Assistant Professor, 医学部, 講師 (80184084)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | gene therapy / atherosclerosis / interferon-gamma / interferon-gamma / STAT3 / 新生内膜増生 / グラフト不全 |
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| Research Abstract |
(1) By using PCR, a soluble mutant INF-gamma receptor (INFGR : Fc) is being constructed by conjugating an extracellular domain of human INF-gamma receptor with human IgG Fc segment
(2) To investage the effects of INF-gamma function blocking on vascular remodeling after vascular injury, INFGR : Fc gene transfer using the naked DNA method to the thigh muscle 2 days before vascular injury of rat carotid artery. INFGR : Fc gene therapy reduced the neointima formation by 40% 14 days after vascular injury. Macrophage and T-cell infiltration were not affected by gene therapy. However, the number of BrdU-positive proliferating smooth muscle cells was significantly decreased by INFGR : Fc-treated rats
(3) Roles of JAK-STAT pathway, the putative pathway which mediates INF-gamma-mediated signaling, were investigated during vascular remodeling after vascular injury by using a dominant negative STAT3 (DNS3) gene transfer. DNS3 gene was transferred immediately after balloon injury by using an adenovirus vector. DNS3 significantly ameliorated neointima formation by reducing proliferation and enhancing apoptosis specifically of neointimal smooth muscle cells
(4) Repeated INFRG : Fc gene transfer into thigh muscle ameliorated the progression of atherosclerotic lesion in the apoE knockout mice
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Report
(3 results)
Research Products
(3 results)
