Objective Serotonin (5-hydroxytrypatmine, 5-HT) regulates diverse processes in both the central nervous system (e.g. cognition, perception, mood, feeding behaviour) and the periphery (e.g. smooth muscle contractility, platelet aggregation). As such, dysregulation in the 5-HT system has been shown to contribute to several pathophysiological states, including depression, migraine headaches, and, more recently, some cardiovascular diseases.During my thesis research with Bryan Roth, we demonstrated that 5-HT, the level s of which are elevated in carcinoid syndrome, causes heart valve fibrosis (i.e. cardiac valvulopathy) via activation of 5-HT2B receptors. An additional cardiovascular complication stemming from 5-HT levels is pulmonary hypertension (PH). Prof. Maroteaux has shown, using genetic and pharmacological approaches, that functional 5-HT2B receptors are required for the development of PH in the hypoxic mouse model of the disease. Also, Prof. Maroteaux's in vivo studies have shown that decreased 5-HT2B receptor function prevents hypoxia-induced increases in plasma 5-HT. Thus, 5-HT2B receptors appear to play an unappreciated role in 5-HT synthesis, release, and/or uptake in the cardiovascular system and likely elsewhere (e.g. the CNS).Indeed, preliminary findings from Prof. Maroteaux's group reveal a role for 5-HT2B receptors in the plasma membrane targeting of the 5-HT transporter (SERT), suggesting that 5-HT2B receptors affect 5-HT levels by modulating SERT function. Thus, Prof. Maroteaux and I propose to characterize, through in vitro and tissue-specific in vivo studies, the mechanism of 5-HT2B receptors regulate SERT function and 5-HT levels in the cardiovascular system. These studies are likely to uncover previously unidentified mechanisms regulating 5-HT in the cardiovascular system; mechanisms that may be pertinent in the CNS. As such, our efforts could lead to novel strategies to treat cardiovascular diseases and, possibly, psychiatric disorders. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesclinical medicinepsychiatrynatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesclinical medicinecardiologycardiovascular diseasesmedical and health sciencesbasic medicinephysiology Keywords 5-HT2B Cardiovascular Depression Pulmonary Hypertension Serotonin Serotonin transporter Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.3 - Marie Curie Incoming International Fellowships (IIF) Call for proposal FP6-2004-MOBILITY-7 See other projects for this call Funding Scheme IIF - Marie Curie actions-Incoming International Fellowships Coordinator INSERM ADR6 ST ANTOINE Address Hôpital saint-antoine, 184, rue du faubourg-saint-antoine, Paris France See on map Links Website Opens in new window EU contribution € 0,00
