Abstract
Acute exposure to hand-arm transmitted vibrations (HAVs) may decrease the wall shear stress (WSS) exerted by the blood flow on the arterial endothelium. In the case of chronic exposure to HAVs, these WSS changes can lead to arterial growth and remodeling potentially induced by an intimal hyperplasia phenomenon. Accordingly, we implemented an agent-based model (ABM) that captures the hemodynamics-driven and mechanoregulated cellular mechanisms involved in vibration-induced intimal hyperplasia. Our ABM was combined with flow loop experiments that investigated the WSS-modulated secretion of the platelet-derived growth factor BB (PDGF-BB) by the endothelial cells. The ABM rules parameters were then identified and calibrated using our experimental findings and literature data. The model was able to replicate the basal state (no vibration) as well as predict a 30% stenosis resulting from a chronic drop of WSS values mimicking exposure to vibration during a timeframe of 10 years. The study of the influence of different WSS-modulated phenomena on the model showed that the magnitude of stenosis largely depends on the migratory effects of PDGF-BB and the mitogenic effects of Transforming Growth Factor \(\beta\) on the Smooth Muscle Cells. The results also proved that the fall in circumferential stress due to arterial layer thickening to a great extent accounts for the degradation of the Extracellular Matrix in the media.
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MR and CN and EJ contributed to conceptualization; MR and CN contributed to formal analysis; CN contributed to funding acquisition; MR and CN contributed to investigation; MR and CN and NS and JC and AL and GR (section 2.3) and EJ contributed to methodology; CN contributed to project administration and resources; MR contributed to software; CN and EJ supervised the study; CN and NS and JC and EJ contributed to validation; MR contributed to visualization and writing-original draft preparation; CN and NS and JC and AL and EJ contributed to writing-review and editing.
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Appendix 1 ABM rules
The biological mechanisms modeled inside the ABM are expressed using mathematical formulations derived from experimental data obtained from our flow loop experiments and from literature data. In all the graphs, the red dots correspond to the experimental data and the solid lines are the fitted models. (see Table 3, 4, 5, 6)
Appendix 2 ABM parameters
See Table 7.
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Reda, M., Noël, C., Settembre, N. et al. An agent-based model of vibration-induced intimal hyperplasia. Biomech Model Mechanobiol 21, 1457–1481 (2022). https://doi.org/10.1007/s10237-022-01601-5
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DOI: https://doi.org/10.1007/s10237-022-01601-5