Impaired mass transfer characteristics of blood borne vasoactive species such
as ATP in regions such as an arterial bifurcation have been hypothesized as a
prospective mechanism in the aetiology of atherosclerotic lesions. Arterial endothelial
(EC) and smooth muscle cells (SMC) respond differentially to altered
local hemodynamics and produce coordinated macro-scale responses via intercellular
communication. Using a computationally designed arterial segment comprising
large populations of mathematically modelled coupled ECs & 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 (Ca2+) 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 Ca2+ coupling between smooth muscle cells is necessary for propagation
of Ca2+ waves from downstream to upstream cells axially. Desynchronized
intracellular Ca2+ oscillations in coupled smooth muscle cells are mandatory for
this propagation. Upon decoupling the heterocellular membrane potential, the
arterial segment looses the inhibitory effect of endothelial cells on the Ca2+ dynamics
of underlying smooth muscle cells. The full system comprising 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.
| Identifer | oai:union.ndltd.org:canterbury.ac.nz/oai:ir.canterbury.ac.nz:10092/6190 |
| Date | January 2011 |
| Creators | Shaikh, Mohsin Ahmed |
| Publisher | University of Canterbury. Centre for Bioengineering |
| Source Sets | University of Canterbury |
| Language | English |
| Detected Language | English |
| Type | Electronic thesis or dissertation, Text |
| Rights | Copyright Mohsin Ahmed Shaikh, http://library.canterbury.ac.nz/thesis/etheses_copyright.shtml |
| Relation | NZCU |
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