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

MacLean, M. (M.) R. (2018) The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series). Pulmonary Circulation, 8(2), pp. 1-9. (doi: 10.1177/2045894018759125) (PMID:29468941)

[img]
Preview
Text
155226.pdf - Published Version
Available under License Creative Commons Attribution.

378kB

Abstract

Increased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The incidence of PAH associated with diet pills such as aminorex, fenfluramine, and chlorphentermine initially led to the “serotonin hypothesis of pulmonary hypertension.” Over the last couple of decades there has been an accumulation of convincing evidence that targeting serotonin synthesis or signaling is a novel and promising approach to the development of novel therapies for PAH. Pulmonary endothelial serotonin synthesis via tryptophan hydroxlase 1 (TPH1) is increased in patients with PAH and serotonin can act in a paracrine fashion on underlying pulmonary arterial smooth muscle cells (PASMCs), In humans, serotonin can enter PASMCs via the serotonin transporter (SERT) or activate the 5-HT1B receptor; 5-HT1B activation and SERT activity cooperate to induce PASMC contraction and proliferation via activation of downstream proliferative and contractile signaling pathways. Here we will review the current status of the serotonin hypothesis and discuss potential and novel therapeutic targets.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLean, Professor Margaret
Authors: MacLean, M. (M.) R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pulmonary Circulation
Publisher:SAGE Publications
ISSN:2045-8932
ISSN (Online):2045-8940
Published Online:22 February 2018
Copyright Holders:Copyright © 2018 The Author
First Published:First published in Pulmonary Circulation 8(2): 1-9
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record