However, there are some suspected differences between the two genetic conditions: both pSMAD2 and pERK1/2 were activated before aneurysms developed, however downstream TGF-β-activated target genes (Fn-1, Pai-1, and Smad7) were not upregulated in Smad3−/− aorta, reflecting the loss of a canonical signaling effector SMAD3. Here, SMAD3 is linked to aneurysm.