Growth arrest of thoracic aortic aneurysms in aging Marfan mice

There remains a pressing need to identify pathologic mechanisms that render a thoracic aortic aneurysm susceptible to continued enlargement, dissection, or rupture, yet additional insight can be gleaned by understanding compensatory mechanisms that limit disease progression and thereby stabilize a lesion. Our biomechanical data suggest that the ascending aorta within a common mouse model of Marfan syndrome, Fbn1C1041G/+, exhibits progressive disease from 12 weeks to 1 year of age but near growth arrest from 1 to 2 years of age. Comparison of the biomechanical phenotype, histological characteristics, and proteomic signature from 12 weeks to 1 year to 2 years plus the transcriptional profile from 12 weeks to 2 years suggests that multiple differentially expressed genes (including downregulated Ltbp3 and Rictor) and associated proteins may contribute to late-term growth arrest. Although there is a need to understand better the interconnected roles of temporal changes in differential gene expression and protein abundance, modulating TGFβ signaling and reducing mTOR signaling appears to merit increased attention in limiting aneurysmal expansion in Marfan syndrome.