Clarification of the Mechanism of Arterial Thrombus Formation by Dynamic Functional Imaging of Platelets

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Since platelet play crucial role in the onset of atherothrombotic diseases including myocardial infarction and ischemic stroke, it is important to understand the mechanism of platelet activation and thrombus formation. For this purpose, real time dynamic and function imaging of platelet is helpful. With the use of ultra-fast laser confocal microscopy equipped with piezo-motor control unit, we have developed a system enabling to visualize three-dimensional growth of platelet thrombi occurring under condition of blood flow. (Goto S, et al. J Am Coll Candiol, 2005 and 2006) We have applied this imaging system for the real time measurement of intracyclic calcium ion concentration by using calcium sensitive fluorenscent dye of Fluo-3 AM. We have demonstrated that the cyclic inflow of calcium through platelet membrane regulated by ADP receptor of P2Y12 was essentially important for the maintenance of the active conformation of GP IIb/IIIa and keep the integrity of platelet thrombi. We have also tried to clarify the interaction of various platelet membrane proteins by multicolor imaging, yet the results have not been published. We have also demonstrated the important role of glycoprotein VI in the formation of platelet thrombosis.Percutaneous cathether mediated thrombus aspiration technique enabled us to obtain sample of thrombi causing myocardial infarction freshly. We have demonstrated the co-localization of platelets and von Willebrand factor, suggesting the causative role of von Willebrand factor in the formation of arterial thrombosis. We have also tried to identify the functional role of von Willebrand factor cleavage protein of ADAMIS13 in the formation of arterial thrombosis.