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


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.
Schaff
Mathieu
M
Inserm Unité Mixte de Recherche-S949, Etablissement Français du Sang-Alsace 10, Strasbourg CEDEX, France.
Receveur
Nicolas
N
Bourdon
Catherine
C
Wurtz
Virginie
V
Denis
Cécile V
CV
Orend
Gertraud
G
Gachet
Christian
C
Lanza
François
F
Mangin
Pierre H
PH
D050197:Atherosclerosis / Q000097:blood* / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D048430:Cell Shape; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000097:blood; D038982:Integrin alpha2beta1 / Q000097:blood; D039661:Integrin beta3 / Q000097:blood; D008562:Membrane Glycoproteins / Q000097:blood; D018715:Microscopy, Video; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D019063:Tenascin / Q000378:metabolism*; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism
D005353:Fibronectins; C056564:ITGA2B protein, human; D039421:Integrin alpha2; D038982:Integrin alpha2beta1; D039661:Integrin beta3; D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D019063:Tenascin; C094990:adhesion receptor; D014841:von Willebrand Factor; D002118:Calcium