Massively Parallel Models for Endothelial /Smooth Muscle Cell coupling in atherosclerotic plaque susceptible vascular geometries
It is well known that atherosclerosis occurs at very specific locations throughout the human vasculature, such as arterial bifurcations and bends, all of which are subjected in some part to low wall shear stress (WSS) and significant variations in surface concentrations of blood borne chemical agonists such as ATP. Orientation (axial alignment) and the size of the interstitial space for endothelial cells varies significantly at arterial bends and bifurcations correlating strongly with the position of atherosclerotic plaque formation. Importantly atherosclerotic lesions occur over a much larger length scale than just a single cell and in some cases these lesions grow ‘upstream’ indicating a phenomenon independent of LDL convection.
Little work has been done to investigate the dynamic relationship between relatively large spatial variations in WSS and ATP concentrations on coupled arrays of both endothelial (ECs) and smooth muscle cells (SMCs). Even though nitric oxide (NO) is not considered to be a dominant parameter in the dynamical system the non-linear interaction of heterogeneously activated cells is crucial to understanding both the natural and pathological functions of the endothelium and underlying SMCs in areas of the vasculature predisposed to atherosclerotic plaque formation. Hence Disruption of inter-cellular coupling between endothelial and smooth muscle cells located in atherosclerotic prone areas of the vasculature (principally arterial bifurcations) is an important factor in atherogenesis. The neuro/cardiovascular group (led by Prof David), comprising 3 post-graduate students and a post-doctoral position has developed several integrated models where complex blood flow and cellular mechanisms interact. In addition it has been able to utilise these cellular models in replicating the coupled SMC work of a number of international workers. Use of Blue Gene (www.bluefern.canterbury.ac.nz ) system at the University of Canterbury has a unique structure ideally suited to coupled arrays of cells (or collections of cells) each simulated by a set of ordinary differential equations. The project will utilise this structure such that The proposed work provides for a full simulation model where the replication of small scale phenomena is mapped onto the large scale fluid dynamics. The simulation of cellular chemistry will be run on the Blue Gene in a unique synchronous way with the fluid dynamics.
Only funded via successful application to University of Canterbury Doctoral Scholarship.