Bifurcation analysis of a model for atherosclerotic plaque evolution

We analyze two ordinary differential equation (ODE) models for atherosclerosis. The ODE models describe long time evolution of plaques in arteries. We show how the dynamics of the first atherosclerosis model (model A) can be understood using codimension-two bifurcation analysis. The Low-Density Lipoprotein (LDL) intake parameter (d) is the first control parameter and the second control parameter is either taken to be the conversion rate of macrophages (b) or the wall shear stress (σ). Our analysis reveals that in both cases a Bogdanov-Takens (BT) point acts as an organizing center. The bifurcation diagrams are calculated partly analytically and to a large extent numerically using AUTO07 and MATCONT. The bifurcation curves show that the concentration of LDL in the plaque as well as the monocyte and the macrophage concentrations exhibit oscillations for a certain range of values of the control parameters. Moreover, we find that there are threshold values for both the cholesterol intake rate dcrit and the conversion rate of the macrophages bcrit, which depend on the values of other parameters, above which the plaque volume increases with time. It is found that larger conversion rates of macrophages lower the threshold value of cholesterol intake and vice versa. We further argue that the dynamics for model A can still be discerned in the second model (model B) in which the slow evolution of the radius of the artery is coupled self-consistently to changes in the plaque volume. The very slow evolution of the radius of the artery compared to the other processes makes it possible to use a slow manifold approximation to study the dynamics in this case. We find that in this case the model predicts that the concentrations of the plaque constituents may go through a period of oscillations before the radius of the artery will start to decrease. These oscillations hence act as a precursor for the reduction of the artery radius by plaque growth.