Different physiologic biomechanical metrics correlate with aortic diameter increases in normal maturation compared to aneurysm progression in mice

Abstract

Thoracic aortic aneurysm (TAA) is the major cardiovascular manifestation of Marfan Syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1. Aneurysmal dilation usually occurs in the ascending aorta (ASC) in MFS, but structural and mechanical changes are detectable throughout the arterial tree that may lead to dissection and rupture. Clinical management includes measuring ASC diameter and/or growth rate but does not typically include other regions of the thoracic aorta and dissection in the descending aorta (DSC) can occur after surgical replacement of the ASC. In severe forms of MFS, dilation forms concomitantly with aortic maturation, so it can be difficult to separate normal and pathologic changes in diameter. We used Fbn1^mgR/mgR (MU) (a model of severe MFS) and wildtype (WT) mice and quantified biaxial physiologic biomechanical metrics of ASC and DSC at 1, 2, 3, and 4 months of age, which includes a period of normal growth and aortic maturation in WT mice and aneurysm formation in MU mice. The results showed age- and location-specific dilation and alterations in biomechanical metrics with different patterns in WT and MU aorta. A multivariable mixed model showed that stored strain energy and circumferential stress were the primary contributors to aortic diameter predictions in WT ASC and DSC, while circumferential and axial incremental moduli (i.e. material stiffness) were the primary contributors to aortic diameter predictions in MU ASC and DSC. The results highlight different biomechanical metrics associated with aortic diameter increases in normal maturation compared to TAA progression in mice.