, Volume 72, Issue 6, pp 1534-1561
Date: 04 May 2010

An ODE Model of Early Stages of Atherosclerosis: Mechanisms of the Inflammatory Response

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Abstract

Atherosclerosis is a chronic disease of the large arteries, characterized by fatty cholesterol-filled streaks and plaque build-up within the artery wall. Within the past decade, inflammation has been determined as a crucial factor in all stages of lesion formation, however, many of the mechanisms involved are not yet fully understood. We present a simplified ODE model that explores the role of inflammation in atherosclerosis. The model incorporates two of the main lesion constituents, cholesterol-carrying modified Low Density Lipoproteins (LDLs) and macrophage foam cells. Their complex interactions are combined into general functions, and the long-term model behaviour is investigated through phase plane analysis and simulations. Our results indicate that the underlying mechanisms of macrophage uptake of modified LDL can have a deep impact on the cellular dynamics in the lesion. Our model demonstrates that it is macrophage proliferation and constant signalling to the endothelial cells, rather than an increasing influx of modified LDL, that drives lesion instability.