| Research Abstract |
In this research project, we have analyzed the shear-dependent functions of von Willebrand factor (VWF) under physiologic blood flow conditions. As a result,
1. Based on the crystal structure analysis of VWF Al domain recently revealed, we analyzed and reconstruct the structure-function relationships for the VWF-GP Ib interaction under physiologic blood flow conditions (Sugimoto M. et al, Int J Hematol, 75:19-24, 2002)
2. Dynamic platelet shape changes and platelet activation mechanisms were analyzed in the platelet adhesive process on immobilized VWF-surface under high shear flow conditions. Unique integrin "inside-out" and "outside-in" signaling mechanisms were discussed (Kuwahara M, Sugimoto M. et al, Arterioscr Thromb Vasc Biol, 22:329-334, 2002)
3. Distinct and concerted adhesive functions of two major adhesive protein, von Willebrand factor and fibrinogen, were visibly revealed in the process of three-dimensional mural thrombus development under high shear flow conditions (Matsui H, Sugimoto M. et al, Blood, 100:36043610, 2002).
4. Molecular Mechanisms of bleeding tendency in type 2A and 2B von Willebrand disease, congenital functional defect of VWF, were analyzed under physiologic blood flow conditions. Shear-dependent functions of high molecular weight multimer of VWF in mural thrombus growth were revealed (Sugimoto M. et al, Blood, 101:915-920, 2003)
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