title: The serotonin pathway in pulmonary hypertension.
abstract: The nature of the primary defect responsible for triggering and maintaining pulmonary artery smooth muscle (PA-SMC) proliferation in pulmonary artery hypertension (PH) is poorly understood but may be either an inherent characteristic of PA-SMCs or a secondary response to an external abnormality, such as up-regulation of growth factors. In previous studies, we found that cultured PA-SMCs from patients with idiopathic PH (iPH) had an abnormally strong proliferative response to serotonin or serum (which contains high levels of serotonin). This abnormal response is due to overexpression of the serotonin transporter (5-HTT) which mediates the mitogenic action of serotonin. That 5-HTT plays a key role in pulmonary vascular remodeling is supported by experimental studies showing that transgenic animals overexpressing 5-HTT in smooth muscle (at a level close to that seen in PH) spontaneously develop pulmonary vascular remodeling and PH. Conversely, mice with targeted S-HTT gene disruption are protected against hypoxic PH, and selective 5-HTT inhibitors reverse or prevent experimental PH. In patients with chronic lung disease, a close association has been found between a 5-HTT gene polymorphism and the severity of pulmonary hypertension. Agents capable of selectively inhibiting 5-HTT-mediated PA-SMC proliferation deserve to be investigated as potential treatments for pulmonary hypertension.
authors.affiliation: INSERM U651, Département de Physiologie, Hôpital Henri-Mondor, Créteil.
authors.forename: S
authors.initials: S
authors.lastname: Eddahibi
authors.forename: S
authors.initials: S
authors.lastname: Adnot
mesh_terms: D000818:Animals; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins