A multiphysics approach for modeling early atherosclerosis

Abstract

This work is devoted to the development of a mathematical model of the early stages of atherosclerosis incorporating processes of all time scales of the disease and to show their interactions. The cardiovascular mechanics is modeled by a fluid-structure interaction approach coupling a non-Newtonian fluid to a hyperelastic solid undergoing anisotropic growth and a change of its constitutive equation. Additionally, the transport of low-density lipoproteins and its penetration through the endothelium is considered by a coupled set of advection-diffusion-reaction equations. Thereby, the permeability of the endothelium is wall-shear stress modulated resulting in a locally varying accumulation of foam cells triggering a novel growth and remodeling formulation. The model is calibrated and applied to an murine-specific case study, and a qualitative validation of the computational results is performed. The model is utilized to further investigate the influence of the pulsatile blood flow and the compliance of the artery wall to the atherosclerotic process. The computational results imply that the pulsatile blood flow is crucial, whereas the compliance of the aorta has only a minor influence on atherosclerosis. Further, it is shown that the novel model is capable to produce a narrowing of the vessel lumen inducing an adaption of the endothelial permeability pattern.

Coronary artery plaque growth: A two‐way coupled shear stress–driven model

“…Compensatory remodeling and expansive remodeling are also possible . To simulate these scenarios, growth and remodeling models need to be developed . Coronary autoregulation in response to a stenosis may affect the peripheral resistance and therefore the flow rate.…”

Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide

“…In atherosclerosis, low‐density lipoproteins (LDLs) in the vascular walls tend to be oxidatively modified. After differentiation from monocytes initially, macrophages can sense and intake the oxidized modified LDLs (ox‐LDL) by the action of cluster of differentiation 36(CD36) and class A1 scavenger receptors (SR‐A1), which are the macrophage scavenger receptors (SRs) with high affinity to sense ox‐LDL (). TMAO plays an important role in augmenting the accumulation of ox‐LDL within macrophages by upregulating the expression of CD36 and SR‐A1 ().…”

A Spatially Resolved and Quantitative Model of Early Atherosclerosis

“…The transport of LDL through the endothelium is well-studied and commonly assessed by the equations of Kedem and Katchalsky [45,103,10,43,74,93,90]. The crucial role of biomechanics in the penetration of LDL is usually incorporated by a WSS-dependent adaption of the Kedem-Katchalsky equations.…”

“…To this end, some researchers model the different LDL transport pathways in full detail and estimate their individual alteration based on local WSS [69,70]. In contrast, other approaches consider only a WSS-dependent hydraulic conductivity [85] or utilize heuristic laws that represent changes in the diffusive permeability [10,93]. These models drastically reduce the complexity but still mimic a physiologically correct behavior.…”

“…Many researchers model the transmural flow across the endothelium and within the artery wall using porous media approaches [74,94,103,70]. Others model the artery wall as an elastic solid and the LDL transport as a purely diffusive process [19,64,27,10,95,93]. The importance of the transmural flow on the endothelial and intimal lipoprotein transport and on early atherosclerosis is controversial [95,70] and is thus addressed in this contribution.…”