PP2A attenuates thoracic aneurysm and dissection in mouse models of Marfan syndrome [RNA-seq]

Recent studies show that hyperactivation of mTOR signaling plays a causal role in the development of thoracic aortic aneurysm (TAA) and dissection (AAD). Modulation of Protein phosphatase 2A (PP2A) activity has been shown to be of significant therapeutic value. In light of the effects that PP2A can exert on mTOR pathway, we hypothesized that PP2A activation by small molecule activators of PP2A (SMAPs) could mitigate AA progression in Marfan Syndrome (MFS). Fbn1mgR/mgR mice, which has under-expression of Fbn1 gene, were obtained from the Jackson Laboratory (JAX stock #005704). A 5mg/kg dose of DT-061 was given orally twice a day to mice starting at the age of 5 weeks (Fbn1mgR/mgR). DT-061 was prepared in a N,N-dimethylacetamide/Kolliphor HS-15/diH20 solution. The control mice were orally given vehicle solution along the same schedule. After 4 weeks of treatment, total RNAs were extracted from ascending aortas in mice and was sent for bulk RAN-seq.