Inserm Unité Mixte de Recherche-S949, Etablissement Français du Sang-Alsace 10, Strasbourg CEDEX, France.
Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):117-24. doi: 10.1161/ATVBAHA.110.206375. Epub 2010 Jul 22.
The identification of platelet-reactive proteins exclusively present in atherosclerotic plaques could provide interesting targets for effective and safe antithrombotic strategies. In this context, we explored platelet adhesion and activation to tenascin-C (TN-C), a matrix protein preferentially found within atheroma.
We show that platelets efficiently adhere to TN-C under both static and flow conditions. Videomicroscopy revealed a unique behavior under flow, with platelets exhibiting stationary adhesion to TN-C; in contrast, platelets rolled over von Willebrand factor and detached from fibrinogen. Platelet interaction with TN-C was predominantly supported by integrin α(2)β(1) under static conditions, whereas under high shear, it was dependent on both the α(2)β(1) integrin and the glycoprotein Ib-IX complex. Integrin α(IIb)β(3) appeared to play a secondary role but only at low shear rates. The glycoprotein Ib-IX-dependent interaction was indirect, relying on von Willebrand factor, and increased as a function of wall shear rate. Von Willebrand factor bound directly to TN-C, as shown by ELISA and coimmunoprecipitation, suggesting that it acts as a bridge between TN-C and platelets. The adhesion of platelets to TN-C triggered their activation, as demonstrated by a shape change and increases in intracellular calcium level.
This study provides evidence that TN-C serves as a novel adhesive matrix for platelets in a context that is relevant to atherothrombosis.
鉴定仅存在于动脉粥样硬化斑块中的血小板反应蛋白，可以为有效和安全的抗血栓形成策略提供有趣的靶点。在这方面，我们研究了血小板在动脉粥样硬化斑块中优先存在的基质蛋白 tenascin-C（TN-C）上的黏附和激活。
我们发现血小板在静态和流动条件下都能有效地黏附在 TN-C 上。视频显微镜显示，在流动条件下，血小板表现出一种独特的黏附行为，血小板在 TN-C 上呈现静止黏附；相比之下，血小板在 von Willebrand 因子上滚动并从纤维蛋白原上脱落。在静态条件下，血小板与 TN-C 的相互作用主要由整合素 α(2)β(1)支持，而在高剪切力下，它依赖于 α(2)β(1)整合素和糖蛋白 Ib-IX 复合物。整合素 α(IIb)β(3)似乎起着次要作用，但仅在低剪切速率下起作用。糖蛋白 Ib-IX 依赖性相互作用是间接的，依赖于 von Willebrand 因子，并随壁剪切率的增加而增加。ELISA 和共沉淀实验表明，von Willebrand 因子直接与 TN-C 结合，表明它作为 TN-C 和血小板之间的桥梁。血小板与 TN-C 的黏附触发了它们的激活，这表现为形态变化和细胞内钙离子水平的增加。
本研究提供了证据表明，TN-C 作为一种新型的血小板黏附基质，在与动脉血栓形成相关的情况下发挥作用。
