Mass Transport of Low Density Lipoprotein in Reconstructed Hemodynamic Environments of Human Carotid Arteries: The Role of Volume and Solute Flux Through the Endothelium

Abstract

The accumulation of low density lipoprotein (LDL) in the arterial intima is a critical step in the initiation and progression of atheromatous lesions. In this study we examine subject-specific LDL transport into the intima of carotid bifurcations in three human subjects using a three-pore model for LDL mass transfer. Subject-specific carotid artery computational models were derived using magnetic resonance imaging (MRI) to obtain the geometry and phase-contract MRI (PC-MRI) to acquire pulsatile inflow and outflow boundary conditions for each subject. The subjects were selected to represent a wide range of anatomical configurations and different stages of atherosclerotic development from mild to moderate intimal thickening. A fluid-solid interaction (FSI) model was implemented in the computational fluid dynamics (CFD) approach in order to consider the effects of a compliant vessel on wall shear stress (WSS). The WSS-dependent response of the endothelium to LDL mass transfer was modeled by multiple pathways to include the contributions of leaky junctions, normal junctions, and transcytosis to LDL solute and plasma volume flux from the lumen into the intima. Time averaged WSS (TAWSS) over the cardiac cycle was computed to represent the spatial WSS distribution, and wall thickness (WTH) was determined from black blood MRI (BBMRI) so as to visualize intimal thickening patterns in the bifurcations. The regions which are exposed to low TAWSS correspond to elevated WTH and higher mass and volume flux via the leaky junctions. In all subjects, the maximum LDL solute flux was observed to be immediately downstream of the stenosis, supporting observations that existing atherosclerotic lesions tend to progress in the downstream direction of the stenosis.

Development of a Patient-Specific Multi-Scale Model to Understand Atherosclerosis and Calcification Locations: Comparison with In vivo Data in an Aortic Dissection

“…The endothelial permeability model proposed here is based on previous work describing the early stages of atherosclerosis, using a transport model of low density lipoprotein (LDL) from the artery lumen into the arterial wall, taking into account the effects of mechanical stimuli exerted by the blood flow on the endothelial cell layer and its pathways of volume and solute flux; see Díaz-Zuccarini et al ( 2014 ) for more details. An excellent and recent analysis and use of this model along the same lines using time-average wall shear stress (TAWSS) has been recently published by Kim and Giddens ( 2015 ).…”

“…We will use a virtual “follow-up” approach, combining a fluid-structure interaction (FSI) simulation model of a dissected aorta with a model of plaque formation, using a number of somewhat disparate indicators available in the literature, which will be described below. The patient-specific simulation results are then coupled to an endothelial permeability model following the three-pore approach (Olgac et al, 2008a ), also recently used by Kim and Giddens ( 2015 ).…”

Endothelial Plasticity: Shifting Phenotypes through Force Feedback

“…For example, despite the fact that most risk factors for atherosclerosis development and progression are present at the systemic level, this inflammatory arterial disease preferentially develops in regions which are characterized by disturbed hemodynamic flow, typically encountered at the outer walls of vascular bifurcations and at the inner wall of vascular curvatures [ 9 , 10 ]. Indeed, disturbances of fluid shear stress levels encountered at these locations are predictors of plaque location [ 11 ], associate with the increased mass transport of low-density lipoproteins (LDL) which build up the plaques [ 12 ], and are major determinants of plaque transition from stable plaques to high-risk unstable plaques and plaque rupture [ 13 ].…”

Computational modeling of geometry effects on the IDL surface concentration in the presence of non-uniform magnetic field – links to atherosclerosis

“…Moreover, the local flow disturbances intensificate the probability of localization and progression of atheroma [26]. There are several studies about mass transport in the vicinity of bifurcation, due to the clinical significance of atherogenesis in bifurcation [27,28].…”