HINT3 and pulmonary arterial hypertension: Our findings can be summarized as follows: (1) both USP11 and HINT3 are regulated at multiple levels, based on concordant elevation of mRNA and protein in the lungs of IPAH patients and hypoxia/Sugen-treated mice with experimental PAH in vivo; (2) however, the balance of ubiquitination and USP11-mediated deubiquitination is a major determinant of HINT3 protein stability; and (3) HINT3 positively regulates the anti-apoptotic mediator BCL2, consistent with the stereotyped finding of apoptosis-resistance in pulmonary artery endothelial cells.