Novel function of tenascin-C, a matrix protein relevant to atherosclerosis, in platelet recruitment and activation under flow.

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)