Recently, reports showed that Tacrolimus, an inhibitor of mTOR, was associated with increased Smad1/5/8 signaling in cultured Alk1 knock-down endothelial cells and in an Alk1−/+ mouse model of HHT and pulmonary arterial hypertension [205, 206]. This evidence concerns the gene ALK and hereditary hemorrhagic telangiectasia.