[Serotonin and pulmonary arterial hypertension].
BACKGROUND
Pulmonary arterial hypertension (PAH) is related to hypertrophic remodelling of the pulmonary vessels. Proliferation of pulmonary vascular smooth muscle cells (PA-SMCs) plays a key role in these changes.


BACKGROUND
The PA-SMCs of patients suffering from idiopathic or secondary PAH are characterized by abnormally increased in vitro proliferation in response to serotonin or serum. Serotonin transporter (5-HTT), the mediator of the mitogenic activity of serotonin, and the expression of which is increased in the course of idiopathic or secondary PAH, is the basis of these effects. The overexpression of 5-HTT, selectively induced in vascular smooth muscle by transgenesis in the mouse, leads to the development of PAH. Treatment with selective 5-HTT inhibitors prevents or leads to complete reversal of experimental hypoxic or inflammatory PAH. The presence of polymorphism of the gene causing over expression of the protein and proliferation of PA-SMCs seems to determine the severity of certain types of human PAH, notably that complicating COPD.


CONCLUSIONS
There is a potential therapeutic application of 5-HTT inhibitors in human PAH. A clinical study is currently taking place in France.


CONCLUSIONS
The exploration of the role of 5-HTT and the mechanisms leading to its overexpression in PAH, as well as the interactions between 5-HTT and the BMPR2 gene, should lead to a significant increase in the understanding of the pathophysiology of the disease.
Eddahibi
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INSERM U651 et Département de Physiologie, Hôpital Henri Mondor, AP-HP, Créteil, France.
Adnot
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D000818:Animals; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index
D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors