NOS2 and pulmonary arterial hypertension: PDE5 inhibitors (such as sildenafil, tadalafil, and vardenafil) have been routinely applied for the treatment of erectile dysfunction, benign prostatic hyperplasia, cardiac hypertrophy, and pulmonary hypertension.258 These inhibitors were also reported to downregulate the expression of ARG1, iNOS, and IL-4Ra in MDSCs via increasing the intracellular cyclic guanosine monophosphate (cGMP) concentrations, thus making MDSCs less immunosuppressive.259,260 One possible molecular mechanism for these effects is that cGMP destabilizes iNOS mRNA by reducing the ubiquitous mRNA binding protein.