The mechanism of platelet thrombus formation at site of endothelial damage under blood flow conditions

血流条件下内皮损伤部位血小板血栓形成机制

• 批准号: 13670744
• 负责人: GOTO Shinya
• 金额: $ 2.56万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670744/
• 关键词: thrombi; platelet; von Willebrand factor; laser confocal microscopy; collagen; matrix; P-selectin; 白血球; 血流; 血管内皮

We investigated the mechanism of platelet thrombus formation at site of functional or mechanical damage of endothelial cells. When blood was perfused on the subendothelial matrix exposed at the site of endoihelial injury, platelets were activated upon interaction with the matrix under blood flow condition. The interaction between von Willebrand factor and its corresponding platelet receptor of glycoprotein (GP) Ibα in addition to the interaction between collagen and GP VI are two most important interaction necessary for platelet activation. The amount of platelets accumulated on the matrix surface increased when stent was placed and blood flow conditions were disturbed.On the cultured endothelial cell surface, it is hard to visualize platelets interacting with endothelial cells even after full activation of them by cytokines. Tissue factor generated from endothelial cells play important roles on the enhancement of platelet thrombi, while it did not directly interact with platelet under blood flow conditions.In conclusion, our newly developed imaging system enabled by ultra-fast laser confocal microscopy was useful to dissect the mechanism of platelet thrombus formation under blood flow conditions.

我们探讨了内皮细胞功能或机械损伤部位的血小板血栓形成机制。当血液灌流到暴露在损伤部位的内皮下基质上时，血小板在血流条件下与基质相互作用而被激活。Von Willebrand因子与其相应的血小板糖蛋白受体(GP)Ibα之间的相互作用以及胶原与GP VI之间的相互作用是血小板活化所必需的两个最重要的相互作用。随着支架置入和血流条件的改变，基质表面聚集的血小板数量增加，在培养的内皮细胞表面，即使在细胞因子完全激活后，也很难观察到血小板与内皮细胞的相互作用。血管内皮细胞产生的组织因子在血小板血栓形成中起重要作用，而在血流条件下，组织因子并不直接与血小板相互作用。综上所述，我们新开发的超快激光共聚焦显微镜成像系统有助于剖析血流条件下血小板血栓形成的机制。

项目成果

後藤信哉: "動脈硬化の発症と進展に関与する血小板と白血球の相互作用の分子機構-血流条件下の検討-"分子循環器研究講演会講演記録集. 9. 31-33 (2001)

Shinya Goto：“参与动脉硬化发生和进展的血小板和白细胞之间相互作用的分子机制 - 血流条件下的检查 -”分子心脏病学研究会议讲座记录 9. 31-33 (2001)。

Sakakibara M: "Application of ex vivo Flow Chamber System for Assessment of Stent Thrombosis"Arteriosclerosis, Thrombosis and Vascular Biology. 22. 1360-1364 (2002)

Sakakibara M：“应用离体流室系统评估支架血栓形成”动脉硬化、血栓形成和血管生物学。

Shinya Goto: "Involvement of Glycoprotein VI in Platelet Thrombus Formation on both Collagen and von Willebrand Factor Surface under Blood Flow Conditions"Circulation. 106. 266-272 (2002)

Shinya Goto：“糖蛋白 VI 参与血流条件下胶原蛋白和血管性血友病因子表面血小板血栓形成”循环。

Li M, et al.: "Specific inhibiting characterization of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine "Chuanxiong", on platelet thrombus formation under high shear rates"Throm Res. 104. 15-28 (2001)

李明等人：“中草药“川芎”的活性成分之一川芎嗪在高剪切速率下对血小板血栓形成的特异性抑制特性”Throm Res。

Li M: "Specific inhibiting characterization of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine "Chuanxiong", on platelet thrombus formation under high shear rates"Thrombosis Research. 104. 15-28 (2001)

李明：“中草药‘川芎’有效成分之一川芎嗪在高剪切速率下对血小板血栓形成的特异性抑制特性”血栓形成研究。