Atherosclerosis is a systemic disease with local manifestations.
Low-density lipoprotein (
LDL) accumulation in the subendothelial layer is one of the hallmarks of
atherosclerosis onset and ignites plaque development and progression. Blood flow-induced endothelial shear stress (ESS) is causally related to the heterogenic distribution of atherosclerotic lesions and critically affects
LDL deposition in the vessel wall. In this work we modeled blood flow and
LDL transport in the coronary arterial wall and investigated the influence of several hemodynamic and
biological factors that may regulate
LDL accumulation. We used a three-dimensional model of a stenosed right coronary artery reconstructed from angiographic and intravascular ultrasound patient data. We also reconstructed a second model after restoring the patency of the stenosed lumen to its nondiseased state to assess the effect of the
stenosis on
LDL accumulation. Furthermore, we implemented a new model for
LDL penetration across the endothelial membrane, assuming that endothelial permeability depends on the local lumen
LDL concentration. The results showed that the presence of the
stenosis had a dramatic effect on the local ESS distribution and
LDL accumulation along the artery, and areas of increased
LDL accumulation were observed in the downstream region where flow recirculation and low ESS were present. Of the studied factors influencing
LDL accumulation, 1)
hypertension, 2) increased endothelial permeability (a surrogate of endothelial dysfunction), and 3) increased serum
LDL levels, especially when the new model of variable endothelial permeability was applied, had the largest effects, thereby supporting their role as major cardiovascular risk factors.