| Project/Area Number |
18591355
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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, Faculty of Medicine, Professor (60150439)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Takanori University of Miyazaki, Faculty of Medicine, Assistant Professor (20315378)
HATAKEYAMA Kinta University of Miyazaki, Faculty of Medicine, Assistant Professor (60325735)
YAMASHITA Atsushi University of Miyazaki, Faculty of Medicine, Assistant Professor (90372797)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | VWF-CP / Adenovirus / Thrombus / Platelet / Smooth muscle cell / 循環器・高血圧 |
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| Research Abstract |
Background ; Platelet-rich thrombus formation is a critical event in the onset of cardiovascular disease. Since von Willebrand factor(VWF)plays a significant role in platelet adhesion and aggregation, its metabolism is important in the regulation of platelet activation and recruitment. VWF is secreted from endothelial cells as a multimers that spontaneously bind the GP Ib-IX complex and aggregate platelets. VWF-cleaving protease (VWF-CP)is essential for preventing platelet aggregation in the normal circulation, by cleaving the multimers of VWF. The present study examines whether VWF-CP 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 VWF-CP (AdVWFCP) and bacterial beta-galactosidase (AdLacZ). Vascular SMCs infected with AdVWFCP expressed significant VWF-CP activity. In contrast, SMCs infected with AdLacZ did not. To investigate the antithrombotic and antiproliferative effects of VWF-CP 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 2 min of occlusive thrombus formation. In contrast, blood flow in AdVWFCP-infected arteries was preserved for at least 5 min during irradiation. In addition, thrombus formation and subsequent neointimal growth were moderately suppressed.
Conclusion ; The local expression of VWF-CP in injured arteries might prevent arterial thrombosis and subsequent neointimal growth.
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