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

Abstract

The extracellular presence of the adenine nucleotides ATP and ADP induces calcium mobilization in vascular endothelial cells (ECs). ATP/ADP concentration at the EC surface is determined by a balance of convective-diffusive transport to and from the EC surface, hydrolysis by ectonucleotidases at the cell surface, and flow-induced ATP release from ECs. Our previous numerical simulations in a parallel plate geometry had demonstrated that flow-induced ATP release has a profound effect on nucleotide concentration at the EC surface. In the present study, we have extended the modeling to probe the impact of flow separation and recirculation downstream of a backward facing step (BFS) on ATP/ADP concentration at the EC surface. The results show that for both steady and pulsatile flow over a wide range of wall shear stresses, the ATP+ADP concentration at the EC surface is considerably lower within the flow recirculation region than in areas of undisturbed flow outside the recirculation zone. Pulsatile flow also leads to sharp temporal gradients in nucleotide concentration. If confirmed experimentally, the present findings suggest that disturbed and undisturbed flow may affect EC calcium mobilization differently. Such differences might, in turn, contribute to the observed endothelial dysfunction in regions of disturbed flow.

Mathematical modelling of fluid transport and its regulation at multiple scales

“…The diffusion of ATP in the extracellular space was modelled as a sink for A6 epithelia (Gheorghiu and Van Driessche, 2004), for retinal astrocytes and Mueller cells (Newman, 2001), and for goldfish hepatocytes (Chara et al, 2009;Pafundo et al, 2008). However, the most important sink in the extracellular space seems to be the ectonucleotidase activity, which has been modelled for blood vessels (Choi et al, 2007), airway epithelia (Zuo et al, 2008) and goldfish hepatocytes (Chara et al, 2009(Chara et al, , 2010Pafundo et al, 2008).…”

Wall shear stress exposure time: a Lagrangian measure of near-wall stagnation and concentration in cardiovascular flows

“…The local transport of several substances near and at the vessel wall are known to influence atherosclerosis progression [56]. For example, previous studies have looked into transport of low density lipoproteins (LDL) [17,20,30,14], high density lipoproteins (HDL) [40,24], oxygen [16,27], nitric oxide (NO) [45,35], monocytes [12,14], and adenine triphosphate ATP and adenine diphosphate ADP [13,15,8] as important mass transport processes involved in atherosclerosis.Intravascular thrombosis is another compelling pathology associated with most cardiovascular diseases where near-wall transport becomes important [7,25]. The trajectories of individual platelets and the accumulation and residence time of chemical solutes including ADP, thrombin, and various blood factors control clot formation.…”

ATP Transport in Saccular Cerebral Aneurysms at Arterial Bends

“…The ATP release strongly depends on the characteristic WSS. The values of the characteristic WSS used in the recent studies 7,9 were ranged from 0.4 to 5.0 Pa. Since the averaged WSS in our aneurysm models is approximately 0.2 Pa, the ratio of the ATP release to the hydrolysis of ATP to ADP at the aneurysmal walls, S/Kc, is less than 10% when the characteristic WSS is higher than 0.6 Pa, where the notation S refers to the ATP release.…”

“…[7][8][9][10]13,21 Physiological pulsatile flow conditions are appropriate to describe blood flows, but computations of unsteady mass transport in pulsatile flows still require large computational load since extremely small computational meshes are needed to resolve high Peclet number transport. 15 Aneurysms develop as a long-term process, where a mean value of mass concentration may be important.…”

“…11,18,35 ATP transport has also been studied in terms of atherosclerosis. [7][8][9][10]13,21,37 Since these species have low diffusion coefficients, the transport processes are modeled by advection-diffusion equation with high Peclet number.…”