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Am J Physiol Heart Circ Physiol 292: H3148-H3157, 2007. First published February 2, 2007; doi:10.1152/ajpheart.01281.2006
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Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model

Nanfeng Sun,1 Nigel B. Wood,1 Alun D. Hughes,2 Simon A. M. Thom,2 and X. Yun Xu1

1Department of Chemical Engineering and 2National Heart and Lung Institute, International Centre for Circulatory Health, Imperial College London, London, United Kingdom

Submitted 22 November 2006 ; accepted in final form 31 January 2007

The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.

low-desity lipoprotein transport; lipid accumulation; atherosclerosis; hypertension



Address for reprint requests and other correspondence: N. Sun, Dept. of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK (e-mail: nanfeng.sun{at}imperial.ac.uk)




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