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

Area of Science:

• Biophysics
• Cardiovascular Biology
• Computational Mechanics

Background:

• Aortic dissections are linked to medial degeneration.
• Understanding the biophysical interactions within the aortic wall's medial layer is crucial.

Purpose of the Study:

• To investigate mechanisms of aortic delamination using Smoothed Particle Hydrodynamics.
• To model the impact of smooth muscle cell (SMC) dysfunction, elastic fiber damage, and glycosaminoglycan (GAG) accumulation on aortic wall integrity.

Main Methods:

• Development of a multi-layered computational model of the healthy aorta.
• Simulation of stress fields resulting from disruptions in elastic lamellae, SMC contractility, and GAG production.
• Analysis of radial load transfer within the aortic medial layer.

Main Results:

• Local elastic lamellar disruptions excessively load adjacent intra-lamellar constituents, increasing cellular vulnerability.
• Impaired SMC function and GAG accumulation elevate mechanical stress on elastic lamellae, promoting further disruption.
• A positive feedback loop between lamellar disruption, cellular dropout, GAG production, and collagen loss is identified, exacerbated by higher pressures.

Conclusions:

• The identified feedback loop can lead to catastrophic intramural delamination, irrespective of the initial trigger.
• Computational modeling provides insights into the mechanical interplay driving aortic medial degeneration and dissection.