Coupled Computational Analysis of Arterial LDL Transport -- Effects of Hypertension

Hypertension, a risk factor for atherosclerosis, increases the uptake of low density lipoproteins (LDL) by the arterial wall. Our objective in this work was to use computational modeling to identify physical factors that could be partially responsible for this effect. Fluid flow and mass transfer patterns in the lumen and wall of an arterial model were computed in a coupled manner, replicating as closely as possible previous experimental studies in which LDL uptake into the artery wall was measured in straight, excised arterial segments. Under conditions of both flow and no-flow, simulations predicted an increase in concentration polarization of LDL at the artery wall when arterial pressure was increased from 120 to 160 mmHg. However, this led to only a slight increase in mean LDL concentration within the arterial wall. However, if the permeability of the endothelium to LDL was allowed to vary with intra-arterial pressure, then the simulations predicted that the uptake of LDL would be enhanced 1.9-2.6 fold at higher pressure. The magnitude of this increase was consistent with experimental data. We conclude that the concentration polarization effects, enhanced by elevated intra-arterial pressure, cannot explain the increase in LDL uptake seen under hypertensive conditions. Instead, the data are most consistent with a pressure-linked increase in endothelial permeability to LDL.