The significant losartaninduced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.
Mice with MFS displayed downstream regulation in both the canonical (Smad2) and noncononical (extracellular signal-regulated kinases and P38) pathways characteristic of MFS.
Dysregulation of the TGF-ß pathway has been implicated in the pathogenesis of inherited disorders predisposing to thoracic aortic aneurysms syndromes (TAAS) including Marfan syndrome (MFS; FBN1) and Loeys-Dietz syndrome (LDS; TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, SMAD3).