The effect of flow-derived mechanical cues on the growth and morphology of platelet aggregates under low, medium, and high shear rates.

Autor: Hao Y; Computational Science Lab, Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands., Tersteeg C; Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium., Hoekstra AG; Computational Science Lab, Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands., Závodszky G; Computational Science Lab, Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands; Department of Hydrodynamic Systems, Budapest University of Technology and Economics, Budapest, Hungary. Electronic address: g.zavodszky@uva.nl.
Jazyk: angličtina
Zdroj: Computers in biology and medicine [Comput Biol Med] 2024 Sep; Vol. 180, pp. 109010. Date of Electronic Publication: 2024 Aug 18.
DOI: 10.1016/j.compbiomed.2024.109010
Abstrakt: Platelet aggregation is a dynamic process that can obstruct blood flow, leading to cardiovascular diseases. While many studies have demonstrated clear connections between shear rate and platelet aggregation, the impact of flow-derived mechanical signals on this process is not fully understood. The objective of this work is to investigate the role of flow conditions on platelet aggregation dynamics, including effects on growth, shape, density composition, and their potential correlation with binding processes that are characterised by longer (e.g., via αIIbβ3 integrin) and shorter (e.g., via VWF) initial binding times. In vitro blood perfusion experiments were conducted at wall shear rates of 800, 1600 and 4000 s -1 . Detailed analysis of two modalities of experimental images was performed to offer insights into the morphology of platelet aggregates. A consistent structural pattern was observed across all samples: a high-density core enveloped by a low-density outer shell. An image-based 3D computational blood flow model was subsequently employed to study the local flow conditions, including binding availability time and flow-derived mechanical signals via shear rate and rate of elongation. The results show substantial dependence of the aggregation dynamics on these flow parameters. We found that the different binding mechanisms that prefer different flow regimes do not have a monotonic cross-over in efficiency as the flow increases. There is a significant dip in the cumulative aggregation potential in-between the preferred regimes. The results suggest that treatments targeting the biomechanical pathways could benefit from creating conditions that exploit these low-efficiency zones of aggregation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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