Dabagh Mahsa, Jalali Payman, Butler Peter J, Randles Amanda, Tarbell John M
Department of Biomedical Engineering, Duke University, Durham, NC, USA
School of Energy Systems, Lappeenranta University of Technology, Lappeenranta, Finland.
J R Soc Interface. 2017 May;14(130). doi: 10.1098/rsif.2017.0185.
Local haemodynamics are linked to the non-uniform distribution of atherosclerosic lesions in arteries. Low and oscillatory (reversing in the axial flow direction) wall shear stress (WSS) induce inflammatory responses in endothelial cells (ECs) mediating disease localization. The objective of this study is to investigate computationally how the flow direction (reflected in WSS variation on the EC surface over time) influences the forces experienced by structural components of ECs that are believed to play important roles in mechanotransduction. A three-dimensional, multi-scale, multi-component, viscoelastic model of focally adhered ECs is developed, in which oscillatory WSS (reversing or non-reversing) parallel to the principal flow direction, or multi-directional oscillatory WSS with reversing axial and transverse components are applied over the EC surface. The computational model includes the glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs), stress fibres and adherens junctions (ADJs). We show the distinct effects of atherogenic flow profiles (reversing unidirectional flow and reversing multi-directional flow) on subcellular structures relative to non-atherogenic flow (non-reversing flow). Reversing flow lowers stresses and strains due to viscoelastic effects, and multi-directional flow alters stress on the ADJs perpendicular to the axial flow direction. The simulations predict forces on integrins, ADJ filaments and other substructures in the range that activate mechanotransduction.
局部血流动力学与动脉粥样硬化病变在动脉中的非均匀分布有关。低且振荡性的（轴向血流方向逆转）壁面剪应力（WSS）在内皮细胞（ECs）中引发炎症反应，介导疾病定位。本研究的目的是通过计算研究血流方向（反映为EC表面WSS随时间的变化）如何影响ECs结构成分所承受的力，这些结构成分被认为在机械转导中起重要作用。建立了一个三维、多尺度、多组分、粘弹性的局部粘附ECs模型，其中在EC表面施加平行于主流方向的振荡性WSS（逆转或非逆转），或具有轴向和横向逆转分量的多向振荡性WSS。计算模型包括糖萼层、肌动蛋白皮质层、细胞核、细胞骨架、粘着斑（FAs）、应力纤维和粘附连接（ADJs）。我们展示了致动脉粥样硬化血流剖面（单向逆转血流和多向逆转血流）相对于非致动脉粥样硬化血流（非逆转血流）对亚细胞结构的不同影响。由于粘弹性效应，逆转血流降低了应力和应变，多向血流改变了垂直于轴向血流方向的ADJs上的应力。模拟预测了整合素、ADJ细丝和其他亚结构上的力处于激活机械转导的范围内。
