Role of the serotonin transporter in pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension is a disease in which pulmonary arterial pressure is raised, leading to right heart failure. Survival is poor despite current therapeutic strategies. The ‘serotonin hypothesis of pulmonary arterial hypertension’ arose in the 1960s following an ‘epidemic’ of pulmonary arterial hypertension in women taking the indirect serotinergic agonist aminorex as an anorexigen. In the 1980s, the hypothesis was revisited following the occurrence of pulmonary arterial hypertension associated with the use of fenfluramines as anorexigens; these are also indirect serotinergic agents. Research has identified changes in serotonin synthesis, serotonin receptor activation and serotonin uptake via the serotonin transporter in experimental and clinical pulmonary arterial hypertension. This review will discuss our current understanding of this serotonin hypothesis with particular reference to the role of the serotonin transporter.

Keywords::

• dexfenfluramine
• pulmonary arterial hypertension
• pulmonary vascular remodeling
• pulmonary vasoconstriction
• selective serotonin-reuptake inhibitors
• serotonin
• serotonin transporter

Financial & competing interests disclosure

The work by MacLean et al. discussed in this review was funded by the British Heart Foundation, Medical Research Council and Biotechnology and Biological Sciences Research Council, UK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.