Mathematical modelling of atherosclerosis as an inflammatory disease.
Atherosclerosis is an inflammatory disease. The atherosclerosis process starts when low-density lipoproteins (LDLs) enter the intima of the blood vessel, where they are oxidized (ox-LDLs). The anti-inflammatory response triggers the recruitment of monocytes. Once in the intima, the monocytes are transformed into macrophages and foam cells, leading to the production of inflammatory cytokines and further recruitment of monocytes. This auto-amplified process leads to the formation of an atherosclerotic plaque and, possibly, to its rupture. In this paper we develop two mathematical models based on reaction-diffusion equations in order to explain the inflammatory process. The first model is one-dimensional: it does not consider the intima's thickness and shows that low ox-LDL concentrations in the intima do not lead to a chronic inflammatory reaction. Intermediate ox-LDL concentrations correspond to a bistable system, which can lead to a travelling wave that can be initiated by certain conditions, such as infection or injury. High ox-LDL concentrations correspond to a monostable system, and even a small perturbation of the non-inflammatory case leads to travelling-wave propagation, which corresponds to a chronic inflammatory response. The second model we suggest is two-dimensional: it represents a reaction-diffusion system in a strip with nonlinear boundary conditions to describe the recruitment of monocytes as a function of the cytokines' concentration. We prove the existence of travelling waves and confirm our previous results, which show that atherosclerosis develops as a reaction-diffusion wave. The results of the two models are confirmed by numerical simulations. The latter show that the two-dimensional model converges to the one-dimensional one if the thickness of the intima tends to zero.
El Khatib
N
N
Institut Camille Jordan, CNRS, UMR 5208, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France. nader@math.univ-lyon1.fr
Génieys
S
S
Kazmierczak
B
B
Volpert
V
V
D050197:Atherosclerosis / Q000276:immunology*; D003198:Computer Simulation; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology; D008955:Models, Cardiovascular; D018448:Models, Immunological; D017539:Tunica Intima / Q000276:immunology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein