What is less clear is: (1) whether the 16α-hydroxylation pathway (i.e., 16αHE1) is a major pathogenic factor in human PAH; (2) whether CYP1B1 activity is directly linked to significant production of 16αHE1; and (3) whether the reported effects are related directly to CYP1B1 modulation of EMet versus the effects of CYP1B1 unrelated to EMet. Here, CYP1B1 is linked to pulmonary arterial hypertension.