| Project/Area Number |
16591212
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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 |
Radiation science
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| Research Institution | University of Miyazaki |
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Principal Investigator |
TAMURA Shozo University of Miyazaki, Department of Radiology, Professor, 医学部, 教授 (60150439)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Takanori University of Miyazaki, Department of Radiology, Assistant Professor, 医学部, 講師 (20315378)
ASADA Yujiro University of Miyazaki, Department of Pathology, Professor, 医学部, 教授 (70202588)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Ecto-NTPDase / Adenovirus / Thrombus / Platelet / ADP / Smooth muscle cell / 血管収縮 / Ecto-ATPDase |
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| Research Abstract |
Background ; Platelet-rich thrombus formation is a critical event in the onset of cardiovascular disease. Since adenosine diphosphate (ADP) plays a significant role in platelet aggregation, its metabolism is important in the regulation of platelet activation and recruitment. Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) is a key enzyme involved in vascular ADP metabolism. We recently isolated two isoforms of E-NTPDase from the human placenta. The present study examines whether these isoforms suppress platelet aggregation and thrombus formation after adenovirus-mediated gene transfer to vascular smooth muscle cells (SMCs).
Methods and Results ; We constructed adenovirus vectors expressing human placental E-NTPDase isoform I (AdPlac I) and II (AdPlac II) or bacterial beta-galactosidase (AdLacZ). Vascular SMCs infected with AdPlac I expressed significant NTPDase activity and inhibited the platelet aggregation induced by ADP and collagen in vitro. In contrast, SMCs infected with AdPlac II and AdLacZ did not exert antiplatelet effects. To investigate the antithrombotic and antiproliferative effects of placental E-NTPDase isoform I in vivo, we generated thrombosis in rat carotid arteries by systemically administered rose bengal and transluminal green light 5 days after gene transfer, and examined neointimal growth 3 weeks after thrombus formation. Blood flow in AdLacZ-infected arteries rapidly deteriorated and vanished within 96+/-18 sec of occlusive thrombus formation. In contrast, blood flow in AdPlac I-infected arteries was preserved for at least 10 min during irradiation. In addition, thrombus formation and subsequent neointimal growth were obviously suppressed.
Conclusion ; The local expression of placental E-NTPDase in injured arteries might prevent arterial thrombosis and subsequent neointimal growth.
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