Project/Area Number |
15390305
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Nara Medical University |
Principal Investigator |
SUGIMOTO Mitsuhiko Nara Medical Univ., Facult. Med., Lecturer, 医学部, 講師 (80192128)
|
Co-Investigator(Kenkyū-buntansha) |
NOGAMI Keiji Nara Medical Univ., Facult. Med., Assistant, 医学部, 助手 (50326328)
朴 永東 奈良県立医科大学, 医学部, 助手 (10285364)
中 宏之 奈良県立医科大学, 医学部, 助手 (40281761)
|
Project Period (FY) |
2003 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥9,100,000 (Direct Cost: ¥9,100,000)
|
Keywords | platelet thrombus formation / blood coagulation / physiologic blood flow / flow chamber / confocal microscopy / 血小板 |
Research Abstract |
Mural thrombus formation at sites of damaged vessel wall, essential for both physiologic hemostasis and pathologic intravascular thrombosis, is established by the concerted function of platelet aggregation and fibrin clot formation. However, most of previous in vitro coagulation assays evaluated fibrin clot formation in a static or closed stirring situation that lacked blood cells including platelets, We have therefore modified a flow chamber system originally established for platelet functional studies, thereby observing the real-time process of intra-thrombus fibrin deposition during platelet thrombus growth under flow conditions. The analysis by confocal laser scanning microscopy in perfusion of whole blood that were anticoagulated to various extents revealed that the development of intra-thrombus fibrin deposition significantly affected the size and shape of individual mural thrombi generated under high shear rate conditions. These observations, reflecting the in vivo comprehensive thrombogeneicity, were further confirmed when heparinized whole blood or whole blood from severe hemophilic patients with or without addition of activated factor VII was perfused. Thus, our experimental approach could help extend understandings for pathogenesis of congenital coagulation disorders as well as for the action mechanisms of various anticoagulants targeting thrombotic diseases, representing the "cell-based coagulation under whole blood flow" that could be most relevant for in vivo hemostasis and thrombosis.
|