Computational Models of Endothelial and Nucleotide Function.
Thesis DisciplineMechanical Engineering
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
Atherogenesis is the leading cause of death in the developed world, and is putting considerable monetary pressure on health systems the world over. Although the risk factors are well understood, unfortunately, the initiation and development of this disease still remains relatively poorly understood, but it is becoming increasingly identifiable as a dysfunction of the endothelial cells that line the walls of arteries. The prevailing haemodynamic environment plays an important role in the focal nature of atherosclerosis to very specific regions of the human vasculature. Disturbed haemodynamics lead to very low wall shear stress, and inhibit the transport of important blood borne chemicals. The present study models, both computationally and mathematically, the transport and hydrolysis of important blood borne adneosine nucleotides in physiologically relevant arterial geometries. In depth analysis into the factors that affect the transport of these low diffusion coefficient species is undertaken. A mathematical model of the complex underlying endothelial cell dynamics is utilised to model production of key intracellular molecules that have been implicated into the complex initiation processes of atherosclerosis; hence regions of the vasculature can be identified as being 'hot spots' for atherogenesis. This model is linked into CFD software allowing for the assessment of how 3D low yields and mass transfer affect the underlying cell signalling. Three studies are undertaken to further understand nucleotide variations at the endothelium and to understand factors involved in determining the underlying cell dynamics. The major focus of the first two studies is geometric variations. This is primarily due to the plethora of evidence implicating the geometry of the human vasculature, hence the haemodynamics, as an influential factor in atherosclerosis initiation. The final model looks at a physiologically realistic geometry to provide a more realistic reproduction of the in vivo environment.