Olgac U, Kurtcuoglu V, Poulikakos D. Computational modeling of coupled blood-wall mass transport of LDL: effects of local wall shear stress. Am J Physiol Heart Circ Physiol 294: H909-H919, 2008. First published December 14, 2007 doi:10.1152/ajpheart.01082.2007.-The work herein represents a novel approach for the modeling of lowdensity lipoprotein (LDL) transport from the artery lumen into the arterial wall, taking into account the effects of local wall shear stress (WSS) on the endothelial cell layer and its pathways of volume and solute flux. We have simulated LDL transport in an axisymmetric representation of a stenosed coronary artery, where the endothelium is represented by a three-pore model that takes into account the contributions of the vesicular pathway, normal junctions, and leaky junctions also employing the local WSS to yield the overall volume and solute flux. The fraction of leaky junctions is calculated as a function of the local WSS based on published experimental data and is used in conjunction with the pore theory to determine the transport properties of this pathway. We have found elevated levels of solute flux at low shear stress regions because of the presence of a larger number of leaky junctions compared with high shear stress regions. Accordingly, we were able to observe high LDL concentrations in the arterial wall in these low shear stress regions despite increased filtration velocity, indicating that the increase in filtration velocity is not sufficient for the convective removal of LDL.low-density lipoprotein transport; lipid accumulation; atherosclerosis; leaky junction MASS TRANSPORT of large molecules such as low-density lipoprotein (LDL) has received considerable interest in recent years because of its significance in the early stages of atherosclerosis. Locally elevated concentrations of LDL in the arterial wall are considered to be the initiator of atherosclerotic plaque formation (20,26). Various experimental (2,19,21,37,38) and computational (1, 13-15, 25, 31, 33, 40) studies have been conducted to comprehend the pathways and mechanisms governing LDL transport from the artery lumen into the arterial wall and within the arterial wall. There are two pathways of LDL transport through the endothelium: by vesicular transcytosis, which is regulated by receptors on the endothelial cells (30), and through leaky junctions, most of which are located at the sites of dying or replicating cells (18,19).Early experimental studies on LDL transport were performed in animals. The main method was systemic injection of LDL solution with subsequent harvesting and examination of the animal's arteries. Lin et al. (19) 2) used endothelial cell cultures to study LDL transport under pressurized conditions and found that LDL transport through leaky junctions constitutes the major part of total LDL transport (90.9%), whereas only a small portion occurs via the vesicular pathway (9.1%). Because the occurrence of leaky junctions is governed by the adjacent endothelial cells, and because the behavior o...