Key result
Platelet VWF deficiency in Nbeal2-/- mice prevents occlusive thrombosis under high shear.
Why the study?
The critical role of platelet von Willebrand factor in occlusive thrombosis formation at high shear was not fully understood.
Platelet α-granule VWF may guide targeted antithrombotic research; leaves open any human therapeutic relevance pending clinical validation.
von Willebrand factor (VWF) is essential for the induction of arterial thrombosis. In this study, we investigated the critical role of platelet VWF in occlusive thrombosis formation at high shear in mice that do not express platelet VWF (Nbeal2-/-). Using in silico modeling, in vitro high-shear microfluidics, and an in vivo Folts model of arterial thrombosis we reproduced the platelet dynamics that occur under pathological flow in a stenosed vessel. Computational fluid dynamics (CFDs) simulated local hemodynamics in a stenosis based on arterial geometries. The model predicted shear rates, time course of platelet adhesion, and time to occlusion. These predictions were validated in vitro and in vivo. Occlusive thrombosis developed in wild-type control mice that had normal levels of plasma VWF and platelet VWF in vitro and in vivo. Occlusive thrombosis did not form in the Nbeal2-/- mice that had normal plasma VWF and an absence of platelet VWF. Occlusive thrombosis was corrected in Nbeal2-/- microfluidic assays by the addition of exogenous normal platelets with VWF. Combining model and experimental data, we demonstrated the necessary requirement of platelet VWF in α-granules in forming an occlusive thrombus under high shear. These results could inspire new pharmacological targets specific to pathological conditions and prevent arterial thrombosis.
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Kim et al. (2020) studied Arterial thrombosis. Absence of platelet VWF (Nbeal2-/- mice) vs. Wild-type control mice was evaluated on Occlusive thrombosis formation at high shear. Occlusive thrombosis did not form in Nbeal2-/- mice lacking platelet von Willebrand factor, whereas it developed in wild-type controls, demonstrating the requirement of platelet VWF in α-granules.
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