[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.