Regulation of transendothelial low-density lipoprotein transmission by fluid shear stress
The link between atherosclerosis and regions of disturbed flow and low wall shear stress is now firmly established, but the causal mechanisms underlying the link are not yet understood. A crucial factor in the early stages of the disease is the blood-to-tissue transport of low-density lipoprotein (LDL). It is well known that a high level of LDL in the blood is a risk factor for atherosclerosis, but the relationship between flow characteristics and LDL transport are not well understood. In this paper, we use a previously derived similarity solution to obtain the concentration profile of LDL at the endothelium, in an arbitrary vessel geometry, in terms of the wall shear stress. The transendothelial transport of LDL is then evaluated downstream of a backward-facing step. It is found that the LDL concentration changes very little over the region of interest and that the main factor in determining the rate of intimal accumulation of LDL is endothelial macromolecular permeability. It is shown that a previously hypothesised dependence of permeability on the spatial gradient of wall shear stress is not necessary to produce higher LDL accumulation in the region of disturbed flow. Experimental data are required to elucidate the precise relationship between wall shear stress and endothelial permeability and the signalling mechanisms involved.
- Engineering: Reports