Consistent with IPAH patient PAECs, when we exposed control p16fl/fl mice (8–10 week old) to hypoxia (8.5% O2) for 3 weeks, p16INK4A mRNA levels increased by 2.1-times in mouse lung ECs compared to that treated with normoxia (Figure 2E). Here, CDKN2A is linked to idiopathic pulmonary arterial hypertension.