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

血小板动态功能成像阐明动脉血栓形成机制

• 批准号: 17590764
• 负责人: GOTO Shinya
• 金额: $ 2.3万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590764/
• 关键词: Platelet; imaging; von Willebrand factor; myocardial infarction; stroke; ADP; 糖タンパク; カルシウム; 凝固系; トロンビン; 膜蛋白; カルシウムシグナル; GPIb; GPIIb; IIIa

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.

由于血小板在动脉粥样硬化性血栓形成疾病包括心肌梗死和缺血性卒中的发病中起着至关重要的作用，因此了解血小板活化和血栓形成的机制是非常重要的。血小板的真实的实时动态和功能显像有助于实现这一目的。使用超快激光共聚焦显微镜配备压电电机控制单元，我们已经开发出一种系统，使可视化三维生长的血小板血栓的条件下发生的血液流动。(Goto S等，J Am科尔Candiol，2005和2006）我们已经应用该成像系统通过使用钙敏感荧光染料Fluo-3 AM来真实的实时测量环内钙离子浓度。研究表明，P2 Y12的ADP受体调控的血小板膜钙循环内流对维持GP IIb/IIIa的活性构象和血小板血栓的完整性具有重要意义。我们也试图通过荧光成像来阐明各种血小板膜蛋白的相互作用，但结果尚未发表。我们还证实了糖蛋白VI在血小板血栓形成中的重要作用。经皮导管介导的血栓抽吸技术使我们能够新鲜获得引起心肌梗死的血栓样品。我们已经证明了血小板和血管性血友病因子的共定位，提示血管性血友病因子在动脉血栓形成中的致病作用。我们还试图确定血管性血友病因子切割蛋白ADVdd 13在动脉血栓形成中的功能作用。

项目成果

臨床現場におけるアスピリン使用の実際

阿司匹林在临床实践中的实际应用

• 发表时间: 2006
• 作者: Uchino T;Lee TS;Kaku T;Yamashita N;Noguchi T;Ono K;Issei Komuro;後藤信哉
• 通讯作者: 後藤信哉

One-Year Cardiovascular Event Rates in the REACH Registry : An International Cohort of Over 68,000 Stable Outpatients with Atherothrombosis.

REACH 登记中的一年心血管事件发生率：超过 68,000 名患有动脉粥样硬化的稳定门诊患者的国际队列。

• 发表时间: 2007
• 期刊: JAMA 297
• 作者: Steg PG;Bhatt DL;Wilson PWF;D'Agostino R;Ohman EM;Rother J;Liau CS;Hirsch AT;Mas JL;Ikeda Y;Pencina MJ;Goto S for the REACH Registry Investigators.
• 通讯作者: Goto S for the REACH Registry Investigators.

A pheochromcytoma causing limited coagulopathy with hemoptysis.

嗜铬细胞瘤引起有限凝血病并伴有咯血。

• 发表时间: 2005
• 期刊: Tokai J Exp Clin Med 30
• 作者: Kimura Y;Ozawa H;Igarashi M;Iwamoto T;Nishiya K;Urano T;Goto S.
• 通讯作者: Goto S.

血栓症ナビケーター

血栓导航仪

• 发表时间: 2006
• 作者: 池田康夫監修;内山真一郎;後藤信哉;重松宏;半田誠編集
• 通讯作者: 半田誠編集

Impact of carotid endarterectomy on medical secondary prevention after a stroke or a transient ischemic attack -: Results from the reduction of atherothrombosis for continued health (REACH) registry

• DOI: 10.1161/01.str.0000249411.44097.5b
• 发表时间: 2006-12-01
• 期刊: STROKE
• 影响因子: 8.3
• 作者: Touze, Emmanuel;Mas, Jean-Louis;Bhatt, Deepak L.
• 通讯作者: Bhatt, Deepak L.