Abstract Number: PB0875
Meeting: ISTH 2022 Congress
Background: Piezo1 is a mechanosensitive cationic channel expressed in many cell types, including blood cells. Piezo1 opens in response to mechanical perturbation of the plasma membrane, resulting in a boost of intracellular [Ca2+]i. Since platelet-driven contraction of blood clots is followed by compression of red blood cells (RBCs), it is conceivable that mechanical activation of Piezo1 in RBCs followed by Ca2+ influx can change cell deformability and/or platelet contractility, thus modulating clot contraction.
Aims: To reveal if Piezo1 channels in RBCs and platelets play a role in the contraction of blood clots.
Methods: Effects of a Piezo1 agonist, Yoda1 (5 μM), and antagonist, GsMTx-4 (1 μM), on clot contraction in vitro were studied in fresh human blood anticoagulated with a corn trypsin inhibitor to keep the physiological [Ca2+]. Clot formation and contraction were induced by thrombin (1 U/ml) either in whole blood or in platelet-rich plasma, and the clot shrinkage was followed using an optical tracking system.
Results: Adding the Piezo1 agonist Yoda1 to whole blood before clotting increased the rate and extent of clot contraction significantly compared to control (p=0.025). In platelet-rich plasma Yoda1 caused the opposite effect, with a moderate decrease in the rate and extent of clot contraction (p=0.06), perhaps by competing with the natural Piezo1 activation in distorted platelets. Adding the Piezo1 antagonist, GsMTx-4, caused a marked decrease in the rate and extent of clot contraction relative to control both in whole blood and in platelet-rich plasma (p=0.0006 and p=0.01, respectively).
Conclusion(s): Activation of Piezo1 channels in RBCs enhances contraction of blood clots, likely mimicking the mechanical activation of Piezo1 in compressed RBCs during platelet-induced clot shrinkage. The subsequent Ca2+ influx in RBCs could affect their rigidity and promote platelet contractility via biomechanical feedback, ATP/ADP release or cause phosphatidylserine exposure followed by enhanced thrombin generation.
To cite this abstract in AMA style:Litvinov R, Evtugina N, Giniatullin R, Weisel J. Mechanosensitive Ion Channels Piezo1 in Red Blood Cells are Involved in Platelet-Driven Blood Clot Contraction [abstract]. https://abstracts.isth.org/abstract/mechanosensitive-ion-channels-piezo1-in-red-blood-cells-are-involved-in-platelet-driven-blood-clot-contraction/. Accessed September 29, 2023.
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