Fibrillar cellular fibronectin supports efficient platelet aggregation and procoagulant activity

Thromb Haemost. 2015 Nov 25;114(6):1175-88. doi: 10.1160/TH14-11-0958. Epub 2015 Aug 6.


The ability of cellular fibronectin, found in the vessel wall in a fibrillar conformation, to regulate platelet functions and trigger thrombus formation remains largely unknown. In this study, we evaluated how parietal cellular fibronectin can modulate platelet responses under flow conditions. A fibrillar network was formed by mechanically stretching immobilised dimeric cellular fibronectin. Perfusion of anticoagulated whole blood over this surface resulted in efficient platelet adhesion and thrombus growth. The initial steps of platelet adhesion and activation, as evidenced by filopodia extension and an increase in intracellular calcium levels (419 ± 29 nmol/l), were dependent on integrins α5β1 and αIIbβ3. Subsequent thrombus growth was mediated by these integrins together with the GPIb-V-IX complex, GPVI and Toll-like receptor 4. The involvement of Toll-like receptor 4 could be conveyed via its binding to the EDA region of cellular fibronectin. Upon thrombus formation, the platelets became procoagulant and generated fibrin as revealed by video-microscopy. This work provides evidence that fibrillar cellular fibronectin is a strong thrombogenic surface which supports efficient platelet adhesion, activation, aggregation and procoagulant activity through the interplay of a series of receptors including integrins α5β1 and αIIbβ3, the GPIb-V-IX complex, GPVI and Toll-like receptor 4.

Keywords: Platelets; arterial thrombosis; fibronectin; haemostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / metabolism
  • Blood Coagulation / physiology*
  • Extracellular Matrix
  • Fibrin / biosynthesis
  • Fibroblasts
  • Fibronectins / chemistry
  • Fibronectins / physiology*
  • Immobilized Proteins
  • Integrin beta1 / genetics
  • Integrins / physiology
  • Lab-On-A-Chip Devices
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfluidic Analytical Techniques
  • Microscopy, Electron, Scanning
  • Platelet Adhesiveness
  • Platelet Aggregation / physiology*
  • Platelet Membrane Glycoprotein IIb / genetics
  • Platelet Membrane Glycoproteins / deficiency
  • Platelet Membrane Glycoproteins / genetics
  • Platelet Membrane Glycoproteins / physiology
  • Rheology
  • Stress, Mechanical
  • Toll-Like Receptor 4 / deficiency
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / physiology


  • Annexin A5
  • Fibronectins
  • Immobilized Proteins
  • Integrin beta1
  • Integrins
  • Platelet Membrane Glycoprotein IIb
  • Platelet Membrane Glycoproteins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • platelet membrane glycoprotein VI
  • Fibrin