Heart disease and calcium signaling in endothelial cells

Endothelial cells (EC), which form the lining of all blood vessels, represent an important signalling unit capable of responding to blood-borne signalling molecules and fluid shear stress. Signal transduction via intracellular messengers such as calcium and IP3 plays a role in regulation of vascular tone and endothelial permeability, factors which affect the likelihood of atherosclerotic plaque formation and heart disease. A mathematical model of the intracellular signalling process, consisting of a number of coupled ordinary differential equations, is presented. The typical response of an EC to an external stimulus is a transient increase in the intracellular free calcium concentration, followed by decay to a plateau level, which persists until the stimulus is removed. However, under certain circumstances, the model exhibits sustained calcium and IP3 oscillations for the duration of the stimulus. The model is coupled to the fluid dynamics in the blood vessel, which affect the concentrations of circulating agonists and the wall shear stress. In this way, the effects of different haemodynamic conditions on endothelial signalling may be examined, improving our understanding of the relationship between vessel geometry and atherosclerosis.