Poster T15 - A Model for Solute Transport across the Arterial Wall

Introduction: The arterial wall is comprised of complex nano and microstructures that play vital roles in the transport of solutes. These nano and microstructural components include endothelial surface glycocalyx (100-400 nm) and tight junctions (10-20nm) between adjacent endothelial cells, the narrow layer of intima (60-200nm) filled with the extracellular matrix, which is sandwiched between the endothelial layer and the internal elastic lamina (IEL). The IEL separates the intima from the tunica media. To understand the mechanism by which these structural components regulate the permeability of the arterial wall, a mathematical model (1-D and 2-D) was developed for solute transport across the arterial wall. Many previous models for the transport across the arterial wall aimed to elucidate the accumulation of macromolecule LDL (radius of 11 nm) in the arterial structure through a leaky endothelial layer for the formation of atherosclerosis. However, the objective of this study is to elucidate the contribution of each structural component of the arterial wall to the solute transport across the arterial wall under normal (intact) conditions. Although endothelial surface glycocalyx has been widely believed to be the molecular sieve for the macromolecules across capillary or postcapillary walls formed by endothelial cells with some pericytes, it is unclear whether it is also the molecular sieve of the arterial wall. Therefore, another objective of this study is to clarify this controversial issue that has lasted for more than two decades.

Materials and

Methods: The model geometry of the arterial wall was constructed based on the anatomical structure from the previous studies including the endothelial surface glycocalyx, inter-endothelial cleft with junction strands, intima layer and the internal elastic lamina (IEL) (Fig. 1). We neglected the media layer due to relatively much less resistance to the transport of under studied macromolecules, albumin with radius 3.5 nm and α-albumin with radius 2 nm. Diffusion equations in each region were solved for the solute transport either analytically for a simplified 1-D model or numerically for a 2-D model using MatLab. The values for the anatomical parameters were obtained from electron microscopy studies in the literature. The solute effective diffusion coefficients in each region with and without fiber matrix were calculated by using the equations from the previous studies.

Results, Conclusions, and Discussions:

Results: 1) Our model predictions match well with the measured permeability of the porcine arterial wall to α-albumin and albumin; 2) Compared to the vessel with the wall formed by endothelium only like capillaries or post-capillary venules, the intima and internal elastic lamina (IEL) of the arterial wall contribute more resistance to the solute transport, about 2.0 and 3.8 folds, respectively, to α-albumin (radius 2 nm) and albumin (radius 3.5 nm); 3) Under normal conditions, the endothelial surface glycocalyx of thickness 100 nm contributes only 5.5% and 5.2% that of the arterial wall resistance to the transport of α-albumin and albumin, respectively. In contrast, this glycocalyx layer contributes ~90% that of the resistance to the transport of albumin across the microvessel wall; 4) The predictions from the simplified 1-D model for the arterial wall permeability to α-albumin and albumin are very close to those predicted by the 2-D model, within 5% differences, due to the narrow structures in the arterial wall, i.e., the length in one direction is 50-200 times that in another direction.

Conclusions: The predictions from our transport model for the arterial wall indicate that 1) the intima and IEL of the arterial wall play a significant role in the modulation of arterial wall permeability and 2) endothelial surface glycocalyx is not the molecular sieve of the arterial wall for macromolecules under physiological conditions.

Acknowledgements (Optional): The study was partially supported by NSF2324052