Patient-specific computational modeling of subendothelial LDL accumulation in a stenosed right coronary artery: effect of hemodynamic and biological factors

摘要

Despite the effect of systemic risk factors, atherosclerosis is a site-specific disease. The localization of early lesions depends on hemodynamic forces, endothelial shear stress (ESS) in particular, which act on the vessel wall (24). In a purely mechanistic viewpoint, low ESS increases the residence time between blood particles [e.g., low-density lipoprotein (LDL)] and the arterial wall and consequently increases the transen-dothelial diffusion and influx. This is in accordance with the higher propensity of atherosclerotic lesions to develop at specific locations in the vasculature, including the lateral walls of arterial bifurcations and the inner side of curved arterial segments, where blood flow is slow and ESS is predominantly low, thereby activating proatherogenic pathways in endothelial cells. Furthermore, changes in local arterial geometry induced by a growing, obstructive plaque have a great impact on the spatial distribution of local ESS. The regional plaque-induced changes of local ESS, in turn, may critically affect the longitudinal distribution of plaque morphology, promoting a self-perpetuating local hemodynamic environment conducive to lipid accumulation and further plaque growth (6, 19).