Modeling lamellar disruption within the aortic wall using a particle-based approach

Abstract

Aortic dissections associate with medial degeneration, thus suggesting a need to understand better the biophysical interactions between the cells and matrix that constitute the middle layer of the aortic wall. Here, we use a recently extended “Smoothed Particle Hydrodynamics” formulation to examine potential mechanisms of aortic delamination arising from smooth muscle cell (SMC) dysfunction or apoptosis, degradation of or damage to elastic fibers, and pooling of glycosaminoglycans (GAGs), with associated losses of medial collagen in the region of the GAGs. First, we develop a baseline multi-layered model for the healthy aorta that delineates medial elastic lamellae and intra-lamellar constituents. Next, we examine stress fields resulting from the disruption of individual elastic lamellae, lost SMC contractility, and GAG production within an intra-lamellar space, focusing on the radial transferal of loading rather than on stresses at the tip of the delaminated tissue. Results suggest that local disruptions of elastic lamellae transfer excessive loads to nearby intra-lamellar constituents, which increases cellular vulnerability to dysfunction or death. Similarly, lost SMC function and accumulations of GAGs increase mechanical stress on nearby elastic lamellae, thereby increasing the chance of disruption. Overall these results suggest a positive feedback loop between lamellar disruption and cellular dropout with GAG production and lost medial collagen that is more pronounced at higher distending pressures. Independent of the initiating event, this feedback loop can catastrophically propagate intramural delamination.

Critical Pressure of Intramural Delamination in Aortic Dissection

“…Although there is a need to study effects of hemodynamic loading, the Gibbs-Donnan swelling pressure due to mucoid materials may be sufficient to initiate the separation of the elastic lamella in such cases of micro-defects. 1,32 With increasing volume of an intramural defect, the concentration of the charges may decrease, resulting in a reduction in swelling pressure. The inverse relation between the critical pressure required for tearing and the size of the false lumen suggests the possibility of the continuation of delamination of larger defects either by elevated blood pressure or the progressive accumulation of mucoid material at higher concentrations.…”

“…In summary, previous computational models (including those based on partition of unity and extended finite elements) have provided considerable insight into the biomechanics of aortic dissection 1,19,33,35,39 as well as the importance of the effects of solid-fluid interactions. 5,13,23 In this paper, we showed further that phase-field based finite element models are able to capture key experimental findings and to reveal important new power-law relations that promise to aid in understanding further the biomechanical mechanisms of initiation and propagation of aortic dissection.…”

Aortic “Disease-in-a-Dish”: Mechanistic Insights and Drug Development Using iPSC-Based Disease Modeling

“…In addition to being a functional benchmark, contraction has the ability to drive maturation. VSMCs contract to counterbalance hemodynamic forces as well as circumferential strain in blood vessels and, in response to these, maintain blood flow and pressure (Zulliger et al, 2004;Alexander and Owens, 2012;Ahmadzadeh et al, 2019). Pulsatile stretch is interpreted by cells through intracellular signaling pathways leading to changes in proliferation, contraction, apoptosis, migration, and ECM remodeling (Haga et al, 2007).…”

In Vitro Measurement of Strain Localization Preceding Dissection of the Aortic Wall Subjected to Radial Tension

“…Experimental studies that focused on ADs permitted to measure strength of dissecting aortic tissues [18][19][20][21][22] subjected to radial tension. Although the radial stress in an elastic cylinder subjected to an inflating pressure is negative, the radial stress can become positive in the aortic wall and possibly induce AD when glycosaminoglycans (GaGs) accumulate in the wall [23,24]. However, to the best of our knowledge, the strain distribution across the aortic wall preceding a dissection has never been measured.…”