The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series)

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Serotonin is often referred to as a 'happy hormone' as it maintains good
mood, well-being and happiness. It is involved in communication between nerve cells and plays a role in sleeping and digestion. However too much serotonin can have pathogenic effects and serotonin synthesis is elevated in pulmonary artery endothelial cells from patients with pulmonary arterial hypertension (PAH). PAH is characterised by elevated pulmonary pressures, right ventricular failure, inflammation and pulmonary vascular remodelling; serotonin has been shown to be associated with these pathologies. The rate limiting enzyme in the
synthesis of serotonin in the periphery of the body is tryptophan hydroxylase 1 (TPH1). TPH1 expression and serotonin synthesis are elevated in pulmonary artery endothelial cells in patients with PAH. The serotonin synthesized in the pulmonary arterial endothelium can act on the adjacent pulmonary arterial smooth muscle cells (PASMCs), adventitial macrophages and fibroblasts, in a paracrine fashion. In humans, serotonin enters PASMCs cells via the serotonin transporter (SERT) and it can co-operate with the 5-HT1B receptor on the plasma membrane; this activates both contractile and proliferative signalling
pathways. The 'serotonin hypothesis of pulmonary hypertension' arose
when serotonin was associated with PAH induced by diet pills such as
fenfluramine, aminorex and chlorphentermine; these act as indirect serotonergic agonists causing release of serotonin from platelets and cells through the SERT. Here the role of serotonin in PAH is reviewed. Targeting serotonin synthesis or signalling is a promising novel alternative approach which may lead to novel therapies for PAH.
Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalPulmonary Circulation
Issue number2
Early online date1 Feb 2018
Publication statusPublished - 30 Apr 2018


  • pulmonary hypertension
  • serotonin
  • pulmonary arterial hypertension


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