Computational multiscale analysis of growth and remodeling in the ascending aorta of the Marfan mouse.

Marfan syndrome, caused primarily by mutations in the fibrillin-1 (FBN1) gene, is associated with progressive dilation of the proximal aorta, with dissection and rupture representing the leading causes of early mortality. A characteristic feature of Marfan-associated aneurysm is fragmentation of elastic fibers; however, the extent to which elastin loss alone can account for the observed geometric and mechanical changes remains unclear. In this study, we use a multiscale computational growth and remodeling framework to determine which geometric and mechanical features of the Marfan aorta can be reproduced by prescribed elastin loss acting through mechanically regulated fiber remodeling and tissue growth. The model couples a discrete fiber network representation of collagen, elastin, and actomyosin with a continuum description of the tissue. It is first calibrated to reproduce experimental measurements in the healthy mouse aorta, and Marfan conditions are then introduced by prescribing graded reductions in elastin content (10-80%). The model reproduces key features of the Marfan aorta, including increased wall thickness and radius, reduced axial stress and stretch, and shifts in pressure-dependent stiffness. Quantitative comparison across multiple metrics shows strong agreement between simulations and experiments, with the lowest error occurring at 29% elastin loss. Within the scope of the model, prescribed elastin loss led to many key structural and mechanical features observed in Marfan aortas, demonstrating the predictive potential of the framework for exploring the mechanical consequences of elastin fragmentation.