Particle-based computational modelling of arterial disease.

Abstract

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.