| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Each of major participants in the human haemostatic system, such as platelets, coagulation, fibrinolysis and vessel wall, interact with and influence each other. At the start of development of thrombus formation, platelets adhere and aggregate at the site of vascular injury. The formed platelet plug is gradually consolidated and stabilized by fibrin network (coagulation). Finally, the sequence in the life cycle of a thrombus is represented by healing of the damaged vessel wall and degradation of the thrombus by the fibrinolytic system. This cascade tries to outline how and to which extent these system interact with the initial thrombus formation. Many scientists and physicians have investigated and are much interested in the processes and interactions involved. Because blood clotting in a vessel can results in ischemia and necrosis of perfused tissues, it is important that haemostatic system is carefully controlled. Moreover, fibrinolytic system is also concerned with proteolytic syste
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m. This phenomenon is recently worth notice on the activation of many physiological agonists, such as VEGF, FGF and TGF-β. In preparing in this issue, we have focused on each section of haemostatic system and sought to provide a useful volume for researchers in this field. In the first article, Matsuno [1] widely describe a role of a 2-antiplasmin (α2-AP) and also mention about a new aspect of fibrinolytic inhibitors. α 2-AP is a specific plasmin inhibitor and its physiological effects are well known on the development and the degradation of thrombus formation. Recently, α 2-AP significantly affects proteolytic formation in vivo and plays a role of vascular remodeling and heart failure via VEGF regulation. Moreover, the phenomena shows the possibility that the other physiological substances are also affected by plasmin. Ueshima and Matsuo [2] focus on the fibrinolytic system in the second article. Fibrinolytic compounds have been used and now the new agents that activate the fibrinolytic system have been clinically applied for the thrombolytic therapy. Recently, some derivatives of t-PA have been developed to obtain the longer half-life than native t-PA and allowed to administrate as the single-bolus. Further, the new fibrin-specific PA such as staphylokinase and bat-PA has been developed. Many attempts have been made to develop the drugs that would induce the release of t-PA from endothelial cells. The article of Oury and Coworkers [3] analysis in details the ADP receptor on platelets. Adenine nucleotides, ADP and ATP, are coreleased from dense granules during platelet activation, as well as from endothelial cells and damaged red blood cells following vascular injury. They focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists, antagonists and inhibitors that allow their pharmacological discrimination. The paper of Ishisaki and Matsuno [4] stresses the current view that TGF-β family seems to plays pivotal roles for the development of atherosclerosis. Especially, TGF-β and activin A play protective roles against the development of atherosclerotic plaques. On the other, bone morphogenetic protein seems to play pivotal roles for the calcification of the atherosclerotic plaques. Moreover, it is debatable whether gene therapy modulating cellular signal transductions of TGF-β family is a useful tool for an inhibition of progression of atherosclerotic disease. Less
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