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Effects of the Haemodynamic Stimulus on the Location of Carotid Plaques Based on a Patient-Specific Mechanobiological Plaque Atheroma Formation Model.

ABSTRACT: In this work, we propose a mechanobiological atheroma growth model modulated by a new haemodynamic stimulus. To test this model, we analyse the development of atheroma plaques in patient-specific bifurcations of carotid arteries for a total time of 30 years. In particular, eight geometries (left or right carotid arteries) were segmented from clinical images and compared with the solutions obtained computationally to validate the model. The influence of some haemodynamical stimuli on the location and size of plaques is also studied. Plaques predicted by the mechanobiological models using the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and a new index proposed in this work are compared. The new index predicts the shape index of the endothelial cells as a combination of TAWSS and OSI values and was fitted using data from the literature. The mechanobiological model represents an evolution of the one previously proposed by the authors. This model uses Navier-Stokes equations to simulate blood flow along the lumen in the transient mode. It also employs Darcy's law and Kedem-Katchalsky equations for plasma and substance flow across the endothelium using the three-pore model. The mass balances of all the substances that have been considered in the model are implemented by convection-diffusion-reaction equations, and finally the growth of the plaques has been computed. The results show that by using the new mechanical stimulus proposed in this study, prediction of plaques is, in most cases, better than only using TAWSS or OSI with a minimal and maximal errors on stenosis ratio of 2.77 and 32.89 %, respectively. However, there are a few geometries in which haemodynamics cannot predict the location of plaques, and other biological or genetic factors would be more relevant than haemodynamics. In particular, the model predicts correctly eleven of the fourteen plaques presented in all the geometries considered. Additionally, a healthy geometry has been computed to check that plaque is not developed with the model in this case.

SUBMITTER: Hernandez-Lopez P

PROVIDER: S-EPMC8236601 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The development of unstable carotid atherosclerotic plaques is associated with the induction of neutrophil extracellular traps (NETs) via the activation of diverse inflammatory mediators in the circulating bloodstream. However, the underlying mechanisms through which NETs influence the microenvironment of atherosclerotic plaques and contribute to the development of unstable carotid plaques remain largely elusive. The objective of this study was to elucidate the role of myeloid differentiation protein 1 (MD-1, LY86)-induced NETs underlying the crosstalk between unstable plaque formation and the plaque microenvironment. We employed bioinformatics analysis to identify key genes associated with carotid-unstable plaque, followed by comprehensive validation using various experimental approaches on tissue specimens and plasma samples classified based on pathological characteristics. Patients with carotid-unstable plaques exhibited elevated plasma concentrations of MD-1 (LY86), while patients with stable plaques demonstrated comparatively lower levels. Furthermore, soluble MD-1 was found to induce the formation of NETs through activation of Toll-like receptor signaling pathway. The proliferative and immature vascularization effects of NETs on endothelial cells, as well as their inhibitory impact on cell migration, are directly correlated with the concentration of NETs. Additionally, NETs were found to activate the NF-κB signaling pathway, thereby upregulating ICAM1, VCAM1, MMP14, VEGFA, and IL6 expression in both Human umbilical vein endothelial cells (HUVECs) and HAECs. Subsequently, a significant increase in intraplaque neovascularization by NETs results in poor carotid plaque stability, and NETs in turn stimulate macrophages to produce more MD-1, generating a harmful positive feedback loop. Our findings suggest that soluble MD-1 in the bloodstream triggers the production of NETs through activation of the Toll-like receptor signaling pathway and further indicate NETs mediate a crosstalk between the microenvironment of the carotid plaque and the neovascularization of the intraplaque region. Inhibiting NETs formation or MD-1 secretion may represent a promising strategy to effectively suppress the development of unstable carotid plaques.

Dataset Information

Effects of the Haemodynamic Stimulus on the Location of Carotid Plaques Based on a Patient-Specific Mechanobiological Plaque Atheroma Formation Model.

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