Serotonin has long been recognized to play an important role in the pathogenesis of pulmonary arterial hypertension. It is thought to promote vasoconstriction and remodel pulmonary vasculature. Increased evidence illuminated the important role of serotonin, as well as its receptor and transporter in pulmonary arterial hypertension (PAH). Serotonin binds to 14 different receptor types, which belong to seven families. Among these receptors, 5-HT1B, 5-HT2A and 5-HT2B may play a role in the pathobiology of PAH. The mitogenic action of serotonin on PASMC is mediated by SERT, which induces internalization of indoleamine. So, the changes of SERT expression or activity are closely linked to the abnormal proliferation of PASMC. It was found that the expression of SERT in the pulmonary artery is increased in patients with pulmonary hypertension. There is a polymorphism in the promoter region of the human SERT gene that alters transcriptional activity. It was suggested that individuals with a high basal level of SERT expression related to presence of the long SERT gene promoter variant may be particularly susceptible to one or more of these potential mechanisms. It is considered that serotonin sub-receptors and SERT play an important role in the development of pulmonary hypertension, and these two components might be potential therapeutic targets of this disease, although further clinical investigation is needed.
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