Concentration of blood-borne agonists at the endothelium

Abstract

The delivery of endothelial ligands and macromolecules, such as lipoproteins, from the circulation to the arterial wall is of central importance in modulating endothelial cell function and physiology and, consequently, in the onset of vascular disease. Given the strong spatial correlation between areas of disturbed blood flow and occurrence of atherosclerotic plaque, a detailed understanding of the effects of different fluid flow characteristics on the delivery of factors in the bloodstream to the endothelium is an essential step towards understanding the observed localization of vascular disease to certain focal sites within the vasculature. In this paper, a model of biochemical mass transport in a two-dimensional flow chamber with spatially varying wall shear stress is presented. The advantage of the relatively simple arterial geometry is that all the essential features of blood flow in vivo are captured, but the underlying effects on mass transport, and, hence, on endothelial cell function, are not masked by complex three-dimensional flow. Indeed, it is demonstrated that a previously derived similarity solution, in terms of the shear stress on the endothelial wall, is an asymptotically close approximation to the exact solution to the advection–diffusion equation. The mathematical analysis is then used to identify fundamental links between the wall shear stress and the distribution of chemical species along the endothelium. The physiological implications of these links are discussed, in particular the location of maximum chemical concentration on the endothelium, which is of great significance to the regulation of intracellular signalling and, consequently, endothelial cell function.

Modulation of ATP/ADP Concentration at the Endothelial Surface by Shear Stress: Effect of Flow Recirculation

“…4,11,25 Therefore, there is a need for elucidating the effect of complex flows on EC-surface ATP/ADP concentration. David 10 and Plank et al 31,32 used a similarity formulation to derive an analytical solution for the ATP/ADP concentration at the EC surface for flow over a backward facing step (BFS); however, the work was confined to steady flow and assumed that the wall shear stress distribution was known. Therefore, the impact of complex flow patterns on adenine nucleotide concentration and how flow unsteadiness modulates this behavior remain incompletely understood.…”

Modulation of ATP/ADP Concentration at the Endothelial Cell Surface by Flow: Effect of Cell Topography

“…The adenine nucleotides ATP and ADP are involved in regulating nitric oxide release and intracellular calcium mobilization in ECs 7 , 24 ; therefore, establishing how flow modulates ATP/ADP concentration at the EC surface is important for understanding flow-mediated mechanotransduction. Previous studies had presented mathematical models for ATP/ADP concentration under steady and pulsatile flow within parallel plate flow chambers as well as geometries that elicit flow disturbance such as backward facing steps 8 , 11 , 14 , 19 , 20 , 25 , 30 and aortic branchings. 9 All previous reports, however, neglected the waviness of the EC surface.…”

Structural and hydrodynamic simulation of an acute stenosis-dependent thrombosis model in mice

“…Under these conditions, blood cells may experience both regions of high shear-rate and, more significantly, zones of recirculating flow, downstream of stenoses. A long standing assumption has been that platelet activation and aggregation within regions of blood flow recirculation is promoted via diffusion and advective transport of blood-borne aggregation agonists, leading to platelet activation (Malcolm and Roach, 1979;Ahmed and Giddens, 1983;Plank et al, 2006). However, advances in intra-vital imaging techniques and the widespread and increasing use of thrombosis models involving rodents have facilitated the study of platelet responses under dynamic and laminar conditions (Reynolds r 1).…”