Mathematical modeling of atherogenesis: Atheroprotective role of HDL

Abstract

Atherosclerosis is a chronic inflammatory cardiovascular disease in which arteries harden through the build-up of plaques. This work is devoted to the mathematical modeling and analysis of the inflammatory process of atherosclerosis. We propose a mathematical model formed by three coupled partial differential equations of reaction-diffusion type. We take into account three key-role players: the inflammatory immune cells, the inflammatory cytokines and the oxidized low density lipoproteins. A stability analysis of the kinetic system is performed. It leads to the presence of three stable fixed points relevant to appropriate biological states of atherogenesis; no inflammation, stabilized inflammation (stable plaque) and advanced inflammation (vulnerable plaque). The cases that may occur are subject to the variation of the parameters values. A detailed discussion showing how the model fits the biological phenomena is then established. We investigate as well the existence of solutions of traveling waves type along with numerical simulations that show the wave propagation in different cases. This shows that the inflammatory process propagates inside the intima as a traveling wave. Then, we consider the effect of high density lipoprotein (HDL) on the atherosclerotic plaque formation. To do that, we elaborate a map that determines the level of risk of plaque formation with respect to the prevalence of HDL in the blood. These results confirm but also generalize previous results published in the literature. They also give a deeper understanding to the propagation of the inflammation inside the artery in terms of the interplay among the different main players in the whole process.