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

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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.