Role of Ecto-ATPDase in the Pathogenesis of Acute Coronary Syndrome
| Project/Area Number |
16590284
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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 |
Human pathology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
ASADA Yujiro University of Miyazaki, Faculty of Medicine, Professor, 医学部, 教授 (70202588)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Kinta University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60325735)
MARUTSUKA Kousuke University of Miyazaki, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00239154)
IMAMURA Takuroh University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60203329)
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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 | Acute coronary syndrome / Ecto-ATPDase / Platelets / Vasoconstriction / Coronary plaque |
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| Research Abstract |
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-ATPDase (CD39) is a key enzyme involved in vascular ADP metabolism. To determine whether the expression of CD39 in coronary atherosclerotic lesions is related to plaque instability and thrombus formation, we immunohistochemically assessed specimens from patients with stable and unstable angina who had undergone directional coronary atherectomy (DCA). CD39 immunoreactivity was decreased in culprit lesions of unstable angina compared with those of stable angina, and reduced in DCA specimens with thrombus formation. These results suggest that CD39 expressed in atheromatous plaques plays an important role in preventing acute coronary syndromes.
Next, we examined whether CD39 suppress platelet aggregation and thrombus formation
… More
after adenovirus-mediated gene transfer to vascular smooth muscle cells (SMCs). We constructed adenovirus vectors expressing CD39 (AdCD39) and bacterial beta-galactosidase (AdLacZ). Vascular SMCs infected with AdCD39 expressed significant ATPDase activity and inhibited the platelet aggregation induced by ADP and collagen in vitro. In contrast, SMCs infected with AdLacZ did not exert antiplatelet effects. To investigate the antithrombotic and antiproliferative effects of CD39 in vivo, we generated thrombosis in rat carotid arteries by an intravenous injection of rose Bengal followed by focal irradiation with transluminal green light after gene transfer, and examined neointimal growth after thrombus formation. Blood flow in carotid arteries infected with AdLacZ rapidly deteriorated and vanished within 96+/-18 sec of occlusive thrombus formation. In contrast, blood flow in arteries infected with AdCD39 was preserved for at least 10 min during irradiation when thrombus formation and subsequent neointimal growth was obviously suppressed. The local expression of placental CD39 in injured arteries might prevent arterial thrombosis and subsequent neointimal growth. Less
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Report
(3 results)
Research Products
(16 results)
