Computational modeling of ATP/ADP concentration at the vascular surface

Vascular endothelial cell (EC) responsiveness to blood flow-derived mechanical forces is important for normal vascular function, and abnormalities in EC mechanotransduction play an important role in vascular pathology. Mobilization of intracellular calcium is one of the early and important responses to flow in ECs. Because the extracellular presence of the adenine nucleotides ATP and ADP induces calcium mobilization in ECs, elucidating how flow regulates EC-surface ATP/ADP concentration is important for understanding the calcium flow response. Experimental measurement of ATP/ADP concentration at the EC surface is very difficult; therefore, efforts have focused on developing mathematical models that describe the effect of flow on the ATP/ADP concentration at the EC surface. This chapter reviews the various models that have been presented to date, highlights the models' essential predictions, discusses the physiological implications of the model results, outlines the model limitations, and proposes some key directions for future modeling.