Computational modelling of atherosclerosis

Abstract

Atherosclerosis is one of the principle pathologies of cardiovascular disease with blood cholesterol a significant risk factor. The World Health Organization estimates that approximately 2.5 million deaths occur annually because of the risk from elevated cholesterol, with 39% of adults worldwide at future risk. Atherosclerosis emerges from the combination of many dynamical factors, including haemodynamics, endothelial damage, innate immunity and sterol biochemistry. Despite its significance to public health, the dynamics that drive atherosclerosis remain poorly understood. As a disease that depends on multiple factors operating on different length scales, the natural framework to apply to atherosclerosis is mathematical and computational modelling. A computational model provides an integrated description of the disease and serves as an in silico experimental system from which we can learn about the disease and develop therapeutic hypotheses. Although the work completed in this area to date has been limited, there are clear signs that interest is growing and that a nascent field is establishing itself. This article discusses the current state of modelling in this area, bringing together many recent results for the first time. We review the work that has been done, discuss its scope and highlight the gaps in our understanding that could yield future opportunities.

A Comparison of Fully-Coupled 3D In-Stent Restenosis Simulations to In-vivo Data

“…Also, the size of this neighbourhood is ultimately arbitrary, selected to be “slightly larger” (in fact, 6% larger) than the sum of the radii of the two interacting cells. Although this inhibition is backed up by biological results (Evans et al, 2008), we need to include more accurate modelling of SMC biology (Parton et al, 2016), for example, mention some recent models for SMC growth), including the response of SMC to transmural pressure (DeMaio et al, 2004). …”

A two-phase model of early fibrous cap formation in atherosclerosis

“…Mathematical modelling of the cellular activity in the vessel wall during atherosclerosis is an area of growing research interest (see Parton et al (2016) for a comprehensive review). To date, however, the vast majority of published models have investigated the actions of monocytes/macrophages in disease initiation (El Khatib et al, 2007;Pappalardo et al, 2008;Cohen et al, 2014;Chalmers et al, 2015;Bhui and Hayenga, 2017) and only a handful have explicitly considered the role of SMCs in plaque progression.…”

A lipid-structured model for macrophage populations in atherosclerotic plaques

“…Many mathematical models divide the macrophage population into "macrophage" and "foam cells". This is true in ODE models [28], spatially resolved PDE models [29][30][31] and other computational models [32]. Yet it is clear that there is a continuous distribution of lipid loads across macrophage populations, stretching from monocytes with low lipid loadings and macrophages that can be labelled as foam cells in atherosclerotic plaques.…”