1 Department of Biomedical Engineering, Yale University , New Haven, CT , USA.
2 Departments of Aerospace Engineering and Engineering Mechanics and Biomedical Engineering, The University of Texas at Austin , Austin, TX , USA.
J R Soc Interface. 2018 Dec 21;15(149):20180616. doi: 10.1098/rsif.2018.0616.
Accumulated glycosaminoglycans (GAGs) can sequester water and induce swelling within the intra-lamellar spaces of the medial layer of an artery. It is increasingly believed that stress concentrations caused by focal swelling can trigger the damage and delamination that is often seen in thoracic aortic disease. Here, we present computational simulations using an extended smoothed particle hydrodynamics approach to examine potential roles of pooled GAGs in initiating and propagating intra-lamellar delaminations. Using baseline models of the murine descending thoracic aorta, we first calculate stress distributions in a healthy vessel. Next, we examine increases in mechanical stress in regions surrounding GAG pools. The simulations show that smooth muscle activation can partially protect the wall from swelling-associated damage, consistent with experimental observations, but the wall can yet delaminate particularly in cases of smooth muscle dysfunction or absence. Moreover, pools of GAGs located at different but nearby locations can extend and coalesce, thus propagating a delamination. These findings, combined with a sensitivity study on the input parameters of the model, suggest that localized swelling can alter aortic mechanics in ways that eventually can cause catastrophic damage within the wall. There is, therefore, an increased need to consider roles of GAGs in aortic pathology.
堆积的糖胺聚糖（GAGs）可以在动脉中层的层间空间中隔离水分并引起肿胀。人们越来越相信，局灶性肿胀引起的应力集中可能会引发胸主动脉疾病中常见的损伤和分层。在这里，我们使用扩展的平滑粒子流体动力学方法进行计算模拟，以研究聚集的 GAG 在引发和传播层间分层中的潜在作用。使用鼠胸降主动脉的基线模型，我们首先计算健康血管中的应力分布。接下来，我们检查 GAG 池周围区域的机械应力增加。模拟表明，平滑肌的激活可以部分保护血管壁免受肿胀相关的损伤，这与实验观察结果一致，但在平滑肌功能障碍或缺失的情况下，血管壁仍可能分层。此外，位于不同但附近位置的 GAG 池可以延伸和合并，从而传播分层。这些发现，结合对模型输入参数的敏感性研究，表明局部肿胀会以最终可能导致壁内灾难性损伤的方式改变主动脉力学。因此，需要更多地考虑 GAG 在主动脉病理学中的作用。
