Thoracic aortic aneurysm (TAA) is associated with Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1. Sexual dimorphism has been recorded for TAA outcomes in MFS, but detailed studies on the differences in TAA progression in males and females and their relationships to outcomes have not been performed. The aims of this study were to determine sex differences in the diameter dilatation, mechanical properties, and extracellular matrix (ECM) remodeling over time in a severe mouse model (Fbn1mgR/mgR = MU) of MFS-associated TAA that has a shortened lifespan. Male and female MU and wildtype (WT) mice were used at 1-4 months of age. Blood pressure and in vivo diameters of the ascending thoracic aorta were recorded using a tail cuff system and ultrasound imaging, respectively. Ex vivo mechanics and ECM remodeling of the aorta were characterized using a biaxial test system and multiphoton imaging, respectively. We showed that mechanical properties, such as structural and material stiffness, and ECM remodeling, such as elastic and collagen fiber content, correlated with diameter dilatation during TAA progression. Male MU mice had accelerated rates of diameter dilatation, stiffening, and ECM remodeling compared to female MU mice that may have contributed to their decreased lifespan. The correlation of mechanical properties and ECM remodeling with diameter dilatation suggest that they may be useful biomarkers for TAA progression. The differences in diameter dilatation and lifespans in male and female MU mice indicate that sex is an important consideration for managing thoracic aortic aneurysm in MFS.
Keywords: female; fibrillin-1; male; passive mechanics; thoracic aortic aneurysm.