Dowding Stewart, Zakkaroff Constantine, Moore Stephen, David Tim
UC High Performance Computing Centre, University of Canterbury, Christchurch, New Zealand.
Department of Accounting and Information Systems, University of Canterbury, Christchurch, New Zealand.
Front Physiol. 2018 Oct 31;9:1528. doi: 10.3389/fphys.2018.01528. eCollection 2018.
This work investigates the effect of arterial bifurcation angulation on atherosclerosis development through 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 Ca 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 Ca 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 Ca 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 Ca wave dynamics and development of atheroprone conditions.
这项工作通过耦合细胞动力学模拟研究了动脉分叉角度对动脉粥样硬化发展的影响。这里提出的计算模型结合了细胞途径、流体动力学以及在人体脉管系统中观察到的生理现实的血管几何形状。耦合细胞模型包括具有离子动力学、异质和同型耦合以及电扩散耦合的内皮细胞（ECs）和平滑肌细胞（SMCs）。在耦合细胞模拟中使用了三种动脉分叉表面模型。在引入腔内激动剂（在这种情况下为ATP）后，所有三种模拟都显示在SMC和EC层中Ca的传播波。在引入ATP浓度后，Ca波立即从高ATP区域向低ATP浓度区域传播，形成波相互作用、碰撞和衰减的复杂模式。这些动态现象会以一系列速度较慢的波重复出现。鉴于动脉粥样硬化斑块的特征长度尺度比单个细胞大得多，这项研究的潜在动机是研究宏观尺度现象。微观尺度动力学是在包含超过一百万个细胞的宏观尺度动脉分叉表面上建模的。这里给出的模拟结果表明，动脉粥样硬化发展的易感性取决于分叉角度。结合文献中报道的结果，模拟结果表明，角度较宽的动脉分叉通过紊乱的血流和较低的SMC Ca浓度，对与动脉粥样硬化发展相关的耦合细胞途径有更显著的影响。结果讨论将本研究的结果置于通过Ca波动力学的频率编码进行信息传输与易患动脉粥样硬化状况发展之间潜在联系的背景下进行考虑。
