Mechanics of ascending aortas from TGF3-1,-2,-3 haploinsufficient mice and elastase-induced aortopathy

Transforming growth factor-beta (TGF3-1, -2, -3) ligands act through a common receptor complex yet each is expressed in a unique and overlapping fashion throughout development. TGF3 plays a role in extra-cellular matrix composition with mutations to genes encoding TGF3 and TGF3 signaling molecules contributing to diverse and deadly thoracic aortopathies common in Loeys-Dietz syndrome (LDS). In this investigation, we studied the TGF3 ligand-specific mechanical phenotype of ascending thoracic aortas (ATA) taken from 4-to-6 months-old Tgfb1+/- , Tgfb2+/-, and Tgfb3+/mice, their wild-type (WT) controls, and an elastase infusion model representative of severe elastolysis. Heterozygous mice were studied at an age without dilation to elucidate potential pre-aortopathic mechanical cues. Our findings indicate that ATAs from Tgfb2+/- mice demonstrated significant wall thickening, a corresponding decrease in biaxial stress, decreased biaxial stiffness, and a decrease in stored energy. These results were unlike the pathological elastase model where decreases in biaxial stretch were found along with increases in diameter, biaxial stress, and biaxial stiffness. ATAs from Tgfb1+/- and Tgfb3+/-, on the other hand, had few mechanical differences when compared to wild-type controls. Although aortopathy generally occurs later in development, our findings reveal that in 4-to-6 month-old animals, only Tgfb2+/- mice demonstrate a significant phenotype that fails to model ubiquitous elastolysis.

Automated summary

This study focused on the role of TGF-β3 ligands in thoracic aortopathies, finding that Tgfb2+/- mice exhibited significant mechanical characteristics, while Tgfb1+/- and Tgfb3+/- showed almost no differences compared to wild-type controls.