MAP3K3 and Marfan syndrome: Activated TGF-β/SMAD signaling has been implicated in the pathophysiology of myxomatous valve formation in both human Marfan syndrome and the Fbn1C1039G/+ Marfan mouse model (3, 7, 8, 39), and has also been recently associated with loss of endothelial MEKK3-KLF2/4 signaling in the vasculature (33).