[Serotonin and the cardiovascular system: role of the serotoninergic 5-HT 2B receptor].
Identification of factors controlling myocardial differentiation and proliferation is of great importance for understanding the pathogenesis of congenital heart diseases. The molecular mechanism by which serotonin (5-hydroxytryptamine, 5-HT) regulates embryonic development of heart and cardiovascular functions remained unknown until recently. Inactivation of the 5-HT2B receptor (5-HT2BR) gene leads to embryonic and neonatal death due to the following defects in the heart: (i) 5-HT2BR mutant embryos exhibit a lack of trabeculae in the heart and a reduction in the expression levels of a tyrosine kinase receptor, ErbB-2, leading to mid-gestation lethality. These in vivo data suggest that the 5-HT2BR coupled to the heterotrimeric G protein Gq uses the signaling pathway of ErbB-2 for cardiac differentiation. (ii) Newborn 5-HT2BR-ko mutant mice exhibit cardiac dilation resulting from contractility and structural deficits at the intercellular junctions between cardiomyocytes. (iii) In adult 5-HT2BR mutant mice, echocardiography and electrocardiography confirm the presence of left ventricular dilation and decreased systolic function. These results constitute the first genetic evidence that 5-HT, via the 5-HT2BR, regulates differentiation and proliferation during development as well as cardiac structure and function in adults.
Launay
Jean-Marie
JM
Laboratoire de Biologie Cellulaire, Faculté de Pharmacie, Université Paris V et Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, 2 rue Ambroise Paré-75010 Paris.
D000818:Animals; D000831:Animals, Newborn; D002311:Cardiomyopathy, Dilated / Q000209:etiology*; D004452:Echocardiography; D004569:Electroencephalography; D005260:Female; D005313:Fetal Death / Q000209:etiology*; D018734:Genes, erbB-2; D006321:Heart / Q000196:embryology* / Q000502:physiology*; D006330:Heart Defects, Congenital / Q000209:etiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009206:Myocardium / Q000166:cytology; D011247:Pregnancy; D044348:Receptors, Serotonin, 5-HT2 / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D015398:Signal Transduction
D044348:Receptors, Serotonin, 5-HT2; D012701:Serotonin