Platelet receptor-mediated mechanosensing and thrombosis

One example demonstrating the significance of studying cell mechanosensing is the platelet-mediated blood clot formation (thrombosis) under shear that causes heart attack and stroke-the No. 1 killer worldwide. As an emerging concept, shear forces generated by the hemodynamic flow disturbances have been shown to promote rapid platelet aggregation, which is usually seen in a narrowing vessel due to a growing thrombus, an atherosclerotic plaque, or an interventional device. Notably, this biomechanical mechanism not only challenges the classic agonist-dependent (biochemical) thrombosis model but also demonstrates resistance to the existing antithrombotic agents. Furthermore, recent studies indicate that this biomechanical platelet aggregation requires the interaction of platelet receptor glycoprotein Ibα (GPIbα) with von Willebrand factor (VWF) in plasma. This chapter will summarize the latest understandings on the platelet mechanosensing principles that center the VWF-GPIbα axis. Clinically, this platelet mechanosensing pathway represents a novel therapeutic target for an anti-thrombotic purpose.