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]. The gene discussed is SMAD1; the disease is pulmonary arterial hypertension.