Abstract 5303: Tenascin-c Supports Human Blood Platelet Adhesion and Activation Under Both Static and Flow Conditions
Targeting platelet activating components preferentially expressed in atherosclerotic plaques could represent an attractive anti-thrombotic strategy. Tenascin-C (TN-C) is an interesting candidate due to its high level of expression in atherosclerotic plaques while it is absent from healthy vessels. The aim of our study was to evaluate the capacity of TN-C to support platelet adhesion and activation. Under static conditions, washed platelets adhered to purified TN-C (1,923±206 platelets/mm2) as efficiently as to fibrinogen (2,010±100 platelets/mm2), a well characterized platelet adhesive protein. Perfusion of hirudinated blood through TN-C-coated (50 μg/mL) micro-capillaries under various shear conditions (300 s−1 to 1,500 s−1) led to efficient capture of individual platelets which did not form aggregates in contrast to the response on a collagen matrix. Interestingly, the number of adherent platelets to TN-C was 3.7 and 1.8 higher than onto fibrinogen and von Willebrand factor (VWF) coated surfaces, respectively. In addition, video-microscopy analysis showed that the vast majority of attached platelets displayed a stationary behavior onto TN-C (86.9±4,1%) whereas they rolled over a VWF matrix (78.7±2,4%) and rapidly detached from fibrinogen (83.1±3,2%). These results suggest that TN-C has higher adhesive properties than VWF and fibrinogen under flow. Adhesion to TN-C under flow required the GPIb-IX complex and integrins αIIbβ3 and β1 as shown by inhibition with blocking antibodies and pharmacological inhibitors. Platelets adherent to TN-C under both static and flow conditions, changed their shape and extended filopodia indicating their activation, which was further confirmed by the observation of a sustained intracellular calcium increase. In conclusion, we provide evidence for the ability of TN-C to support platelet adhesion and activation under static and flow conditions indicating a novel putative role in thrombosis. Its presence in atherosclerotic plaques and its implication in platelet recruitment suggest that TN-C could represent a target for anti-thrombotic drugs.