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Coronary Smooth Muscle Cell Calcium Dynamics: Effects of Bifurcation Angle on Atheroprone Conditions.

Abstract：

:This work investigates the effect of arterial bifurcation angulation on atherosclerosis development through in-silico simulations of coupled cell dynamics. The computational model presented here combines cellular pathways, fluid dynamics, and physiologically-realistic vessel geometries as observed in the human vasculature. The coupled cells model includes endothelial cells (ECs) and smooth muscle cells (SMCs) with ion dynamics, hetero and homotypic coupling, as well as electro-diffusive coupling. Three arterial bifurcation surface models were used in the coupled cells simulations. All three simulations showed propagating waves of Ca2+ in both the SMC and EC layers, following the introduction of a luminal agonist, in this case ATP. Immediately following the introduction of ATP concentration Ca2+ waves propagate from the area of high ATP toward the areas of low ATP concentration, forming complex patterns where waves interact with eachother, collide and fade. These dynamic phenomena are repeated with a series of waves of slower velocity. The underlying motivation of this research was to examine the macro-scale phenomena, given that the characteristic length scales of atherosclerotic plaques are much larger than a single cell. The micro-scale dynamics were modeled on macro-scale arterial bifurcation surfaces containing over one million cells. The results of the simulations presented here suggest that susceptibility to atherosclerosis development depends on the bifurcation angulation. In conjunction with findings reported in the literature, the simulation results demonstrate that arterial bifurcations containing wider angles have a more prominent influence on the coupled cells pathways associated with the development of atherosclerosis, by means of disturbed flow and lower SMC Ca2+ concentrations. The discussion of the results considers the findings of this research within the context of the potential link between information transport through frequency encoding of Ca2+ wave dynamics and development of atheroprone conditions.

journal_name

Front Physiol

journal_title

Frontiers in physiology

authors

Dowding S,Zakkaroff C,Moore S,David T

doi

10.3389/fphys.2018.01528

subject

Has Abstract

pub_date

2018-10-31 00:00:00

pages

1528

issn

1664-042X

journal_volume

pub_type

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Coronary Smooth Muscle Cell Calcium Dynamics: Effects of Bifurcation Angle on Atheroprone Conditions.