Patient-specific three-dimensional simulation of LDL accumulation in a human left coronary artery in its healthy and atherosclerotic states

Abstract

We calculate low-density lipoprotein (LDL) transport from blood into arterial walls in a three-dimensional, patient-specific model of a human left coronary artery. The in vivo anatomy data are obtained from computed tomography images of a patient with coronary artery disease. Models of the artery anatomy in its healthy and diseased states are derived after segmentation of the vessel lumen, with and without the detected plaque, respectively. Spatial shear stress distribution at the endothelium is determined through the reconstruction of the arterial blood flow field using computational fluid dynamics. The arterial endothelium is represented by a shear stress-dependent, three-pore model, taking into account blood plasma and LDL passage through normal junctions, leaky junctions, and the vesicular pathway. Intraluminal pressures of 70 and 120 mmHg are employed as the normal and hypertensive operating pressures, respectively. By applying our model to both the healthy and diseased states, we show that the location of the plaque in the diseased state corresponds to one of the two sites with predicted high-LDL concentration in the healthy state. We further show that, in the diseased state, the site with high-LDL concentration has shifted distal to the plaque, which is in agreement with the clinical observation that plaques generally grow in the downstream direction. We also demonstrate that hypertension leads to increased number of regions with high-LDL concentration, elucidating one of the ways in which hypertension may promote atherosclerosis.