A mathematical model of atherogenesis as an inflammatory response

Abstract

We construct a mathematical model of the early formation of an atherosclerotic lesion based on a simplification of Russell Ross' paradigm of atherosclerosis as a chronic inflammatory response. Atherosclerosis is a disease characterized by the accumulation of lipid-laden cells in the arterial wall. This disease results in lesions within the artery that may grow into the lumen restricting blood flow and, in critical cases, can rupture causing complete, sudden occlusion of the artery resulting in heart attack, stroke and possibly death. It is now understood that when chemically modified low-density lipoproteins (LDL cholesterol) enter into the wall of the human artery, they can trigger an immune response mediated by biochemical signals sent and received by immune and other cells indigenous to the vasculature. The presence of modified LDL can also corrupt the normal immune function triggering further immune response and ultimately chronic inflammation. In the construction of our mathematical model, we focus on the inflammatory component of the pathogenesis of cardiovascular disease (CVD). Because this study centres on the interplay between chemical and cellular species in the human artery and bloodstream, we employ a model of chemotaxis first given by E. F. Keller and Lee Segel in 1970 and present our model as a coupled system of non-linear reaction diffusion equations describing the state of the various species involved in the disease process. We perform numerical simulations demonstrating that our model captures certain observed features of CVD such as the localization of immune cells, the build-up of lipids and debris and the isolation of a lesion by smooth muscle cells.

The Apoe-/- Mouse PhysioLab® Platform: A Validated Physiologically-based Mathematical Model of Atherosclerotic Plaque Progression in the Apoe-/- Mouse

“…Some of these models have been customized with individual patient data [32,33]. Other models have incorporated the role of inflammation [34,35]. Plaque progression has also been investigated using agent-based [36] and ODE approaches [37].…”

Mathematical modeling and simulation of the evolution of plaques in blood vessels

“…In the model of Ibragimov et al [31] , a system of six PDEs is used to describe the chemotactic activity of immune cells (primarily macrophages), smooth muscle cells, chemoattractant and low density lipoproteins (LDL); numerical simulations are performed to demonstrate that this model captures certain observed features of cardiovascular disease such as the localization of immune cells, the build-up of lipids and the isolation of a lesion by smooth muscle cells. On the other hand, the model of Ougrinovskaia et al [41] is reduced to a spatially independent ODE, which focuses on how the macrophages take up LDL, and this model's results indicate that it is macrophage proliferation and constant signalling to the endothelial cells, rather than an increase in influx of LDL, that drives lesion instability.…”

GRID Computing and Computational Immunology

“…We presented studies on the increased atherosclerosis risk using an ABM model of atherogenesis and its induced immune system response in humans. Very few mathematical models (Cobbold et al, 2002;Ibragimov et al, 2005) and (to our best knowledge) no computational models of atherogenesis have been developed to date. It is well known that the major risk in atherosclerosis is persistent high level of LDL concentration.…”