S. Génieys

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.

Reaction–diffusion model of atherosclerosis development

Atherosclerosis begins as an inflammation in blood vessel walls (intima). The inflammatory response of the organism leads to the recruitment of monocytes. Trapped in the intima, they differentiate into macrophages and foam cells leading to the production of inflammatory cytokines and further recruitment of white blood cells. This self-accelerating process, strongly influenced by low-density lipoproteins (cholesterol), results in a dramatic increase of the width of blood vessel walls, formation of an atherosclerotic plaque and, possibly, of its rupture. We suggest a 2D mathematical model of the initiation and development of atherosclerosis which takes into account the concentration of blood cells inside the intima and of pro- and anti-inflammatory cytokines. The model represents a reaction–diffusion system in a strip with nonlinear boundary conditions which describe the recruitment of monocytes as a function of the concentration of inflammatory cytokines. We prove the existence of travelling waves described by this system and confirm our previous results which suggest that atherosclerosis develops as a reaction–diffusion wave. The theoretical results are confirmed by the results of numerical simulations.

INTERACTION OF THERMAL EXPLOSION AND NATURAL CONVECTION: CRITICAL CONDITIONS AND NEW OSCILLATING REGIMES ∗

In this paper we investigate, numerically as well as analytically, the influence of natural convection on thermal explosion in a two-dimensional square vessel, filled with a reactant mixture, whose vertical walls are adiabatic and horizontal walls are infinitely conducting, preset at an equal temperature T0 . Natural convection enhances the heat losses at the boundaries while large temperatures tend to promote natural convection, thus yielding two competitive phenomena. The governing equations are taken to be the Navier--Stokes equations in the Oberbeck--Boussinesq approximation of low density variations coupled to the heat equation with an exponential chemical source term. This is valid because we consider a 1-step reaction with high heat release, we use the Frank-Kamenetskii transformation under high activation energy asymptotics, and we do not take into account thermo-diffusion as well as the different molar masses of the species. We solve the vorticity-stream function-temperature formulation with an a...