We have demonstrated that hypoxia-induced PH phenotype was attenuated in p16iΔEC mice (Figures 2, 3) and knock down of p16INK4A inhibits increases in the levels of TWIST1 in hypoxia-treated mouse lungs and IPAH patient PAECs (Figure 3). This evidence concerns the gene TWIST1 and idiopathic pulmonary arterial hypertension.