Serotonin can activate pulmonary arterial fibroblasts and promote adventitia fibrosis through signaling of the TGFβ1/Smad3 pathway27 and, in PASMCs, through NADPH oxidase (Nox)1.28 An interplay between PDGF and serotonin pathways within PAH has also been demonstrated to explain TPH1-dependent imatinib efficacy in collagen-mediated mechanisms of fibrosis.29 Serotonin also activates immune responses and inflammation in many peripheral diseases30 and these effects may also play a role in the development of PAH. This evidence concerns the gene SMAD3 and pulmonary arterial hypertension.