Novel Function of Tenascin-C, a Matrix Protein Relevant to Atherosclerosis, in Platelet Recruitment and Activation Under Flow
| Autor: | Gertraud Orend, Catherine Bourdon, Mathieu Schaff, Virginie Wurtz, Pierre Mangin, Nicolas Receveur, François Lanza, Christian Gachet, Cécile V. Denis |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Platelets
Pathology medicine.medical_specialty Time Factors Integrin Integrin alpha2 Fibrinogen Platelet Adhesiveness Von Willebrand factor Platelet adhesiveness von Willebrand Factor medicine Humans Platelet Platelet activation Cell Shape Membrane Glycoproteins Microscopy Video biology Chemistry Tenascin C Integrin beta3 Tenascin Atherosclerosis Platelet Activation Fibronectins Cell biology Platelet Glycoprotein GPIb-IX Complex Regional Blood Flow biology.protein Calcium Glycoprotein Ib-IX-V Receptor Complex Stress Mechanical Integrin alpha2beta1 Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 31:117-124 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.110.206375 |
| Popis: | Objective— 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. Methods and Results— 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. Conclusion— This study provides evidence that TN-C serves as a novel adhesive matrix for platelets in a context that is relevant to atherothrombosis. |
| Databáze: | OpenAIRE |
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