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

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590764
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tokai University
• Principal Investigator: GOTO Shinya Tokai University, School of Medicine, Department of Medicine, MD., Associate professor, 医学部, 助教授 (50225653)
• Project Period (FY): 2005 – 2006
• Keywords: Platelet / imaging / von Willebrand factor / myocardial infarction / stroke / ADP

Research Abstract

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.

Research Products

• [Journal Article] One-Year Cardiovascular Event Rates in the REACH Registry : An International Cohort of Over 68,000 Stable Outpatients with Atherothrombosis. (2007)
  • Author(s): 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.
  • Journal Title: JAMA 297 Pages: 1197-1206
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] for the REACH Registry Investigators. One-Year Cardiovascular Event Rates in the REACH Registry : An International Cohort of Over 68,000 Stable Outpatients with Atherothrombosis. (2007)
  • Author(s): 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
  • Journal Title: JAMA 297 Pages: 1197-1206
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of a patient with glycoprotein (GP) VI deficiency possessing neither anti-GPVI autoantibody nor genetic aberration. (2006)
  • Author(s): Kojima H, Moroi M, Jung SM, Goto S, Tamura N, Kozuma Y, Suzukawa K, Nagasawa T
  • Journal Title: Journal of Thrombosis and Hemostasis 4・11 Pages: 2433-2442
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 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. (2006)
  • Author(s): Touze E, Mas JL, Rother J, Goto S, Hirsch AT, Ikeda Y, Liau CS, Magnus Ohman E, Richard AJ, Wilson PW, Gabriel Steg P, Bhatt DL, For the REACH Investigators
  • Journal Title: Stroke 37 Pages: 2880-2885
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The REduction of Atherothrombosis for Continued Health (REACH) Registry : An international, prospective, observational investigation in subjects at risk for atherothrombotic events-study design. (2006)
  • Author(s): Ohman EM, Bhatt DL, Steg PG, Goto S, Hirsch AT, Liau CS, Mas JL, Richard AJ, Rother J, Wilson PWF, on behalf of the REACH Registry Investigators.
  • Journal Title: Am Heart J. 2006; : 786.e1-786.e10.. 151
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of a patient with glycoprotein (GP) VI deficiency possessing neither anti-GPVI autoantibody nor genetic aberration. (2006)
  • Author(s): Kojima H, Moroi M, Jung SM, Goto S, Tamura N, Kozuma Y, Suzukawa K, Nagasawa T.
  • Journal Title: J Thromb Haemost. 4(11) Pages: 2433-42
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] For the REACH Investigators. 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. (2006)
  • Author(s): Touze E, Mas JL, Rother J, Goto S, Hirsch AT, Ikeda Y, Liau CS, Magnus Ohman E, Richard AJ, Wilson PW, Gabriel Steg P, Bhatt DL.
  • Journal Title: Stroke 37 Pages: 2880-2885
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] on behalf of the REACH Registry Investigators. The REduction of Atherothrombosis for Continued Health (REACH) Registry : An international, prospective, observational investigation in subjects at risk for atherothrombotic events-study design. (2006)
  • Author(s): Ohman EM, Bhatt DL, Steg PG., Goto S, Hirsch AT, Liau CS, Mas JL, Richard AJ, Rother J, Wilson PWF
  • Journal Title: Am Heart J. 151 Pages: 786.e1-786.e10.
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 臨床現場におけるアスピリン使用の実際 (2006)
  • Author(s): 後藤信哉
  • Total Pages: 1-146
  • Publisher: 南江堂
  • Description: 「研究成果報告書概要(和文)」より