Abstract
Impaired mass transfer characteristics of blood-borne vasoactive species such as adenosine triphosphate in regions such as an arterial bifurcation have been hypothesized as a prospective mechanism in the aetiology of atherosclerotic lesions. Arterial endothelial cells (ECs) and smooth muscle cells (SMCs) respond differentially to altered local haemodynamics and produce coordinated macro-scale responses via intercellular communication. Using a computationally designed arterial segment comprising large populations of mathematically modelled coupled ECs and SMCs, we investigate their response to spatial gradients of blood-borne agonist concentrations and the effect of micro-scale-driven perturbation on the macro-scale. Altering homocellular (between same cell type) and heterocellular (between different cell types) intercellular coupling, we simulated four cases of normal and pathological arterial segments experiencing an identical gradient in the concentration of the agonist. Results show that the heterocellular calcium (Ca(2+)) coupling between ECs and SMCs is important in eliciting a rapid response when the vessel segment is stimulated by the agonist gradient. In the absence of heterocellular coupling, homocellular Ca(2+) coupling between SMCs is necessary for propagation of Ca(2+) waves from downstream to upstream cells axially. Desynchronized intracellular Ca(2+) oscillations in coupled SMCs are mandatory for this propagation. Upon decoupling the heterocellular membrane potential, the arterial segment looses the inhibitory effect of ECs on the Ca(2+) dynamics of the underlying SMCs. The full system comprises hundreds of thousands of coupled nonlinear ordinary differential equations simulated on the massively parallel Blue Gene architecture. The use of massively parallel computational architectures shows the capability of this approach to address macro-scale phenomena driven by elementary micro-scale components of the system.