| dc.description.abstract | Since first being described in 1948, serotonin (5-hydroxytryptamine, 5-HT) has been discovered to exert effects on a vast array of organs and bodily functions. Cardiovascular effects of serotonin were observed in vivo shortly thereafter, but knowledge about the biochemical processes on receptor level was lacking. By the early 1990s, technological advances had led to the discovery of several families and subtypes of the serotonin receptor, and several lines of research were started to assess the effects of serotonin on the fetal and adult heart. Serotonin was, through the 5-HT2B receptor, found to play a vital part in the cardiac embryogenesis, by instigating migratory, morphogenic and trophic responses in the developing heart. In a mouse model, deletion of the gene coding for the 5-HT2B receptor was associated with an increase in perinatal mortality. Overstimulation of the 5-HT2B receptor in the adult human heart has been shown to induce cardiac valvulopathies, particularly in the form of regurgitations, and ventricular hypertrophy, with subsequent cardiac fibrosis, predisposing heart failure. Results have shown that the 5-HT4 receptor is of particular importance in cardiac remodeling following manifest heart failure, with the receptor being upregulated and its inotropic effect potentiated, thus increasing myocardial oxygen consumption. Based on experimental findings, it has been hypothesized that selective serotonin antagonism might prove beneficial in the failing heart. However, preliminary experimental studies in animals have shown a lesser treatment effect than expected. Similar results were shown in a clinical trial of a 5-HT4 antagonist, and no use has been found for serotonin antagonism in a clinical setting thus far. | eng |