An ODE Model of Early Stages of Atherosclerosis: Mechanisms of the Inflammatory Response
- 497 Downloads
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.
KeywordsAtherosclerosis Inflammatory response Macrophages ODE model Dynamical system
Unable to display preview. Download preview PDF.
- Kharbanda, R., MacAllister, R., 2005. The atherosclerosis time-line and the role of the endothelium. Curr. Med. Chem. 5, 47–52. Google Scholar
- Kunjathoor, V.V., Febbraio, M., Podrez, E.A., Moore, K.J., Andersson, L., Koehn, S., Rhee, J.S., Silverstein, R., Hoff, H.F., Freeman, M.W., 2002. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J. Biol. Chem. 277(51), 49982–49988. CrossRefGoogle Scholar
- Lusis, A.J., 2000. Atherosclerosis. Nature 407. Google Scholar
- Prosi, M., Zunino, P., Perktold, K., Quarteroni, A., 2005. Mathematical and numerical models for transfer of low-density lipoproteins through the arterial walls: a new methodology for the model set up with applications to the study of disturbed lumenal flow. J. Biomech. 38, 903–917. CrossRefGoogle Scholar