von Willebrand factor unfolding mediates platelet deposition in a model of high-shear thrombosis

Zhussupbekov, Mansur; Rojano, Rodrigo Méndez; Wu, Wei‐Tao; Antaki, James F.

doi:10.1016/j.bpj.2022.09.040

Cited by 11 publications

(4 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also present a snapshot of the deposited platelet mass, the concentration profiles of soluble platelet agonists ADP and thromboxane, and the velocity profile along a central slice of the stenosis after 180 − s in Figures 7C-F. We note that platelet aggregation is significantly higher near the apex of the stenosis where the observed shear rates experienced by the platelets are highest, a feature that is consistent with prior published computational models and experimental observations [6,9,15,[37][38][39]. This observation is due to the role of VWF in mediating platelet adhesion at high shear rates.…”

Section: Benchmark Simulation Of Human Stenotic Thrombus Growth From ...supporting

confidence: 86%

“…Consequently, computational modeling, specifically multiscale modeling has emerged as a powerful tool for investigating the underlying mechanisms of thrombus growth under flow [2 -15]. Several of these models make use of a continuum approach where platelets, platelet agonists, and coagulation factors are treated as chemical species that obey the convection-diffusion-reaction equation for species transport [11][12][13][14][15]. This approach overcomes the significant computational burden associated with explicitly resolving individual blood cells and accounting for molecular-level interactions between these cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development of a parallel multiscale 3D model for thrombus growth under flow

Shankar,

Diamond,

Sinno

2023

Front. Phys.

View full text Add to dashboard Cite

Thrombus growth is a complex and multiscale process involving interactions spanning length scales from individual micron-sized platelets to macroscopic clots at the millimeter scale. Here, we describe a 3D multiscale framework to simulate thrombus growth under flow comprising four individually parallelized and coupled modules: a data-driven Neural Network (NN) that accounts for platelet calcium signaling, a Lattice Kinetic Monte Carlo (LKMC) simulation for tracking platelet positions, a Finite Volume Method (FVM) simulator for solving convection-diffusion-reaction equations describing agonist release and transport, and a Lattice Boltzmann (LB) flow solver for computing the blood flow field over the growing thrombus. Parallelization was achieved by developing in-house parallel routines for NN and LKMC, while the open-source libraries OpenFOAM and Palabos were used for FVM and LB, respectively. Importantly, the parallel LKMC solver utilizes particle-based parallel decomposition allowing efficient use of cores over highly heterogeneous regions of the domain. The parallelized model was validated against a reference serial version for accuracy, demonstrating comparable results for both microfluidic and stenotic arterial clotting conditions. Moreover, the parallelized framework was shown to scale essentially linearly on up to 64 cores. Overall, the parallelized multiscale framework described here is demonstrated to be a promising approach for studying single-platelet resolved thrombosis at length scales that are sufficiently large to directly simulate coronary blood vessels.

show abstract

Section: Benchmark Simulation Of Human Stenotic Thrombus Growth From ...supporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Development of a parallel multiscale 3D model for thrombus growth under flow

Shankar,

Diamond,

Sinno

2023

Front. Phys.

View full text Add to dashboard Cite

show abstract

“…Under these conditions, platelet thrombus formation is dominated by VWFdependant interactions, mainly via GPIb-V-IX. Aggregates emerge from soluble VWF multimers, which are in their complete unfolded and fibrous conformation (Figure 5) (Zhussupbekov et al, 2022). The fibres easily bind to already adhered and tethered platelets on immobilized VWF forming a net on the surface.…”

Section: 23mentioning

confidence: 99%

Design of artificial vascular devices: Hemodynamic evaluation of shear-induced thrombogenicity

Feaugas

Newman²,

Calzuola³

et al. 2023

Front. Mech. Eng.

View full text Add to dashboard Cite

Blood-circulating devices such as oxygenators have offered life-saving opportunities for advanced cardiovascular and pulmonary failures. However, such systems are limited in the mimicking of the native vascular environment (architecture, mechanical forces, operating flow rates and scaffold compositions). Complications involving thrombosis considerably reduce their implementation time and require intensive anticoagulant treatment. Variations in the hemodynamic forces and fluid-mediated interactions between the different blood components determine the risk of thrombosis and are generally not taken sufficiently into consideration in the design of new blood-circulating devices. In this Review article, we examine the tools and investigations around hemodynamics employed in the development of artificial vascular devices, and especially with advanced microfluidics techniques. Firstly, the architecture of the human vascular system will be discussed, with regards to achieving physiological functions while maintaining antithrombotic conditions for the blood. The aim is to highlight that blood circulation in native vessels is a finely controlled balance between architecture, rheology and mechanical forces, altogether providing valuable biomimetics concepts. Later, we summarize the current numerical and experimental methodologies to assess the risk of thrombogenicity of flow patterns in blood circulating devices. We show that the leveraging of both local hemodynamic analysis and nature-inspired architectures can greatly contribute to the development of predictive models of device thrombogenicity. When integrated in the early phase of the design, such evaluation would pave the way for optimised blood circulating systems with effective thromboresistance performances, long-term implantation prospects and a reduced burden for patients.

show abstract

“…These models handle the thrombus' mechanical properties using an energy functional without explicit reference to bond formation and breaking. The effect of vWF elongation is included indirectly in a twophase continuum model of thrombus formation [22] by increasing the rate of platelet binding to and decreasing the rate of platelet detaching from the thrombus where flow conditions suggest that a large portion of vWF molecules would likely be in a stretched configuration. The binding and unbinding rates of platelets in that study are described using empirical functions.…”

Section: Introductionmentioning

confidence: 99%

A computational investigation of occlusive arterial thrombosis

Du,

Fogelson

2023

Biomech Model Mechanobiol

View full text Add to dashboard Cite

The generation of occlusive thrombi in stenotic arteries involves the rapid deposition of millions of circulating platelets under high shear flow. The process is mediated by the formation of molecular bonds of several distinct types between platelets; the bonds capture the moving platelets and stabilize the growing thrombi under flow. We investigated the mechanisms behind occlusive thrombosis in arteries with a two-phase continuum model. The model explicitly tracks the formation and rupture of the two types of interplatelet bonds, the rates of which are coupled with the local flow conditions. The motion of platelets in the thrombi results from competition between the viscoelastic forces generated by the interplatelet bonds and the fluid drag. Our simulation results indicate that stable occlusive thrombi form only under specific combinations for the ranges of model parameters such as rates of bond formation and rupture, platelet activation time, and number of bonds required for platelet attachment.

show abstract

von Willebrand factor unfolding mediates platelet deposition in a model of high-shear thrombosis

Cited by 11 publications

References 102 publications

Development of a parallel multiscale 3D model for thrombus growth under flow

Development of a parallel multiscale 3D model for thrombus growth under flow

Design of artificial vascular devices: Hemodynamic evaluation of shear-induced thrombogenicity

A computational investigation of occlusive arterial thrombosis

Contact Info

Product

Resources

About