Abstract | 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. CONCLUSIONS: This study provides evidence that TN-C serves as a novel adhesive matrix for platelets in a context that is relevant to atherothrombosis.
|
Authors | Mathieu Schaff, Nicolas Receveur, Catherine Bourdon, Virginie Wurtz, Cécile V Denis, Gertraud Orend, Christian Gachet, François Lanza, Pierre H Mangin |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 31
Issue 1
Pg. 117-24
(Jan 2011)
ISSN: 1524-4636 [Electronic] United States |
PMID | 20651280
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Fibronectins
- ITGA2B protein, human
- Integrin alpha2
- Integrin alpha2beta1
- Integrin beta3
- Membrane Glycoproteins
- Platelet Glycoprotein GPIb-IX Complex
- Tenascin
- adhesion receptor
- von Willebrand Factor
- Calcium
|
Topics |
- Atherosclerosis
(blood, physiopathology)
- Blood Platelets
(metabolism)
- Calcium
(blood)
- Cell Shape
- Fibronectins
(metabolism)
- Humans
- Integrin alpha2
(blood)
- Integrin alpha2beta1
(blood)
- Integrin beta3
(blood)
- Membrane Glycoproteins
(blood)
- Microscopy, Video
- Platelet Activation
- Platelet Adhesiveness
- Platelet Glycoprotein GPIb-IX Complex
(metabolism)
- Regional Blood Flow
- Stress, Mechanical
- Tenascin
(metabolism)
- Time Factors
- von Willebrand Factor
(metabolism)
|