The expression of HIF-1α is diminished in PASMCs from IPAH patients.113 This results in increased expression of miR-543, which subsequently upregulates Twist1 and enhances the expression of ET-1, ultimately promoting vasoconstriction.113 In patients with IPAH, elevated levels of O2 and ascorbate lead to increased PHD activity and reduced HIF-1α protein levels. This evidence concerns the gene EDN1 and idiopathic pulmonary arterial hypertension.