A Roy1, N J Brand, M H Yacoub. 1. Department of Cardiothoracic Surgery, Imperial College School of Medicine, National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Middlesex, UK.
Abstract
BACKGROUND AND AIM OF THE STUDY: Severe heart valve disorder has been reported in patients receiving a combination of the anorectic drugs fenfluramine and phentermine. The exact molecular mechanisms involved remain unknown. Fenfluramine alters the serotonin level in the brain, while phentermine interferes with the pulmonary clearance of serotonin; these data suggest that serotonin levels affect regulation of valve function. The aim of the present study was to characterize the serotonin receptor (5-hydroxytryptamine) subtypes expressed in the interstitial cells of human heart valves. METHODS: Interstitial cells were isolated and cultured from the aortic, pulmonary, mitral and tricuspid valves of recipient hearts obtained during transplantation. Total RNA was extracted from cultured cells in order to determine gene expression by reverse transcription-polymerase chain reaction (RT-PCR) using 5-hydroxytryptamine (5-HT) subtype-specific primer pairs. RESULTS: The results show that: (i) 5-HT 1B and 1D receptor subtypes are expressed in all four heart valves. This is significant as the 1B and 1D receptor subfamilies are the target of the anti-migraine drug sumatriptan, and these receptors regulate cardiac function and movement; (ii) 5-HT 1A, 5-HT 1E and 5-HT 1F are not expressed in interstitial cells isolated from the valves. CONCLUSION: We conclude that preliminary evidence exists for the presence of distinct subsets of 5-HT receptors in human heart valves, indicating that interstitial cells of the valves potentially respond to serotonin levels.
BACKGROUND AND AIM OF THE STUDY: Severe heart valve disorder has been reported in patients receiving a combination of the anorectic drugs fenfluramine and phentermine. The exact molecular mechanisms involved remain unknown. Fenfluramine alters the serotonin level in the brain, while phentermine interferes with the pulmonary clearance of serotonin; these data suggest that serotonin levels affect regulation of valve function. The aim of the present study was to characterize the serotonin receptor (5-hydroxytryptamine) subtypes expressed in the interstitial cells of human heart valves. METHODS: Interstitial cells were isolated and cultured from the aortic, pulmonary, mitral and tricuspid valves of recipient hearts obtained during transplantation. Total RNA was extracted from cultured cells in order to determine gene expression by reverse transcription-polymerase chain reaction (RT-PCR) using 5-hydroxytryptamine (5-HT) subtype-specific primer pairs. RESULTS: The results show that: (i) 5-HT 1B and 1D receptor subtypes are expressed in all four heart valves. This is significant as the 1B and 1D receptor subfamilies are the target of the anti-migraine drug sumatriptan, and these receptors regulate cardiac function and movement; (ii) 5-HT 1A, 5-HT 1E and 5-HT 1F are not expressed in interstitial cells isolated from the valves. CONCLUSION: We conclude that preliminary evidence exists for the presence of distinct subsets of 5-HT receptors in human heart valves, indicating that interstitial cells of the valves potentially respond to serotonin levels.
Authors: Jie Xu; Bo Jian; Richard Chu; Zhibin Lu; Quanyi Li; John Dunlop; Sharon Rosenzweig-Lipson; Paul McGonigle; Robert J Levy; Bruce Liang Journal: Am J Pathol Date: 2002-12 Impact factor: 4.307
Authors: Bo Jian; Jie Xu; Jeanne Connolly; Rashmin C Savani; Navneet Narula; Bruce Liang; Robert J Levy Journal: Am J Pathol Date: 2002-12 Impact factor: 4.307
Authors: W Kocha; J Maroun; H Kennecke; C Law; P Metrakos; J F Ouellet; R Reid; C Rowsell; A Shah; S Singh; S Van Uum; R Wong Journal: Curr Oncol Date: 2010-06 Impact factor: 3.677