{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:26:55Z","timestamp":1791210415481,"version":"4.1.0"},"reference-count":30,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:p>Decreasing the bioavailability of serotonin (5-HT) by inhibiting its biosynthesis may represent a useful adjunctive treatment of pulmonary hypertension (PH). We assessed this hypothesis using LP533401, which inhibits the rate-limiting enzyme tryptophan hydroxylase 1 (Tph1) expressed in the gut and lung, without inhibiting Tph2 expressed in neurons. Mice treated repeatedly with LP533401 (30\u2013250 mg\/kg per day) exhibited marked 5-HT content reductions in the gut, lungs, and blood, but not in the brain. After a single LP533401 dose (250 mg\/kg), lung and gut 5-HT contents decreased by 50%, whereas blood 5-HT levels remained unchanged, suggesting gut and lung 5-HT synthesis. Treatment with the 5-HT transporter (5-HTT) inhibitor citalopram decreased 5-HT contents in the blood and lungs but not in the gut. In transgenic SM22-5-HTT+ mice, which overexpress 5-HTT in smooth muscle cells and spontaneously develop PH, 250 mg\/kg per day LP533401 or 10 mg\/kg per day citalopram for 21 days markedly reduced lung and blood 5-HT levels, right ventricular (RV) systolic pressure, RV hypertrophy, distal pulmonary artery muscularization, and vascular Ki67-positive cells ( P &lt; 0.001). Combined treatment with both drugs was more effective in improving PH-related hemodynamic parameters than either drug alone. LP533401 or citalopram treatment partially prevented PH development in wild-type mice exposed to chronic hypoxia. Lung and blood 5-HT levels were lower in hypoxic than in normoxic mice and decreased further after LP533401 or citalopram treatment. These results provide proof of concept that inhibiting Tph1 may represent a new therapeutic strategy for human PH.<\/jats:p>","DOI":"10.1152\/ajplung.00049.2012","type":"journal-article","created":{"date-parts":[[2012,7,14]],"date-time":"2012-07-14T10:13:52Z","timestamp":1342260832000},"page":"L500-L508","source":"Crossref","is-referenced-by-count":35,"title":["Inhibition of gut- and lung-derived serotonin attenuates pulmonary hypertension in mice"],"prefix":"10.1152","volume":"303","author":[{"given":"Shariq","family":"Abid","sequence":"first","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Houssaini","sequence":"additional","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Chevarin","sequence":"additional","affiliation":[{"name":"U894 INSERM-CPN\/UPMC, Facult\u00e9 de M\u00e9decine Pierre et Marie Curie, site Piti\u00e9-Salp\u00eatri\u00e8re, Paris;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Marcos","sequence":"additional","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire-Marie","family":"Tissot","sequence":"additional","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Gary-Bobo","sequence":"additional","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wan","sequence":"additional","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Mouraret","sequence":"additional","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Amsellem","sequence":"additional","affiliation":[{"name":"INSERM U955 Team 8 and D\u00e9partement de Physiologie, H\u00f4pital Henri Mondor, AP-HP, Cr\u00e9teil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Dubois-Rand\u00e9","sequence":"additional","affiliation":[{"name":"Service de Cardiologie &amp; 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