Abstract Number: PB1693
Meeting: ISTH 2020 Congress
Theme: Platelets and Megakaryocytes » Platelet Function and Interactions
Background: Conformational changes of von Willebrand factor (VWF) molecules play a key role in initiating shear-induced platelet activation (SIPAct). The globule-stretch transition occurs under high shear stress and facilitates the interaction of VWF A1 domains with GPIb receptors on a platelet surface. Multivalent binding leads to the priming of platelets and their consequent activation. The described mechanism was investigated under steady shear stress conditions. However, a shear stress level under a broad range of pathophysiological conditions highly varies. Therefore, for the estimation of platelet activation, it is necessary to take into account not only the shear stress level but also the time of its action. The concept of cumulative shear stress as a measure of the action of shear stress on the platelets along the trajectory in blood flow was suggested.
Aims: The aim of the work was to develop an approach for estimation of platelet activation due to unfolding of VWF on its surface under dynamic shear stress.
Methods: The mathematical model was proposed for the describing of VWF conformational changes on a platelet surface. The dynamics of VWF conformational changes under shear stress influence was investigated analytically and numerically. The methods of nonlinear dynamics were used for analyzing the conditions of VWF unfolding.
Results: The explicit dependence of the critical cumulative shear stress on VWF multimer length was derived. The minimal level of dynamic shear stress below which SIPAct never occurs regardless of exposure time was established.
Conclusions: The obtained results open new possibilities for rational regulation of SIPAct not only by controlling of biomechanical factors, but also pharmacologically by influencing on VWF size distribution.
The work was supported by grant No 19-11-00260 of Russian Science Foundation.
To cite this abstract in AMA style:
Salikhova T, Pushin D, Zlobina K, Guria G. Platelet Interactions with von Willebrand Factor under Dynamic Shear Stress [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelet-interactions-with-von-willebrand-factor-under-dynamic-shear-stress/. Accessed March 22, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-interactions-with-von-willebrand-factor-under-dynamic-shear-stress/