{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:47:09Z","timestamp":1791085629880,"version":"4.1.0"},"reference-count":24,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p> There is substantial evidence supporting a hypertrophic action of serotonin [5-hydroxytryptamine (5-HT)] in cardiomyocytes. However, little is known about the mechanisms involved. We previously demonstrated that 5-HT-induced hypertrophy depends, in part, on the generation of reactive oxygen species by monoamine oxidase-A (MAO-A) (see Ref. 3 ). Cardiomyocytes express 5-HT<jats:sub>2<\/jats:sub> receptors, which may also participate in hypertrophy. Here, we analyzed the respective contribution of 5-HT<jats:sub>2<\/jats:sub> receptors and MAO-A in H9C2 cardiomyoblast hypertrophy. 5-HT induced a dose-dependent increase in [<jats:sup>3<\/jats:sup>H]leucine incorporation and stimulation of two markers of cardiac hypertrophy, ANF-luc and \u03b1SK-actin-luc reporter genes. Experiments using 1 \u03bcM 5-HT showed that hypertrophic response occurred independently from MAO-A. Using pharmacological inhibitors (M100907 and ketanserin), we identified a novel mechanism of action involving 5-HT<jats:sub>2A<\/jats:sub> receptors and requiring Ca<jats:sup>2+<\/jats:sup>\/calcineurin\/nuclear factor of activated T-cell activation. The activation of this hypertrophic pathway was fully prevented by 5-HT<jats:sub>2A<\/jats:sub> inhibitors and was unaffected by MAO inhibition. When 10 \u03bcM 5-HT was used, an additional hypertrophic response, prevented by the MAO inhibitors pargyline and RO 41-1049, was observed. Unlike the 5-HT<jats:sub>2A<\/jats:sub>-receptor-mediated H9C2 cell hypertrophy, MAO-A-dependent hypertrophic response required activation of extracellular-regulated kinases. In conclusion, our results show the existence of a dose-dependent shift of activation of distinct intracellular pathways involved in 5-HT-mediated hypertrophy of cardiac cells. <\/jats:p>","DOI":"10.1152\/ajpheart.00345.2009","type":"journal-article","created":{"date-parts":[[2009,6,19]],"date-time":"2009-06-19T22:09:57Z","timestamp":1245449397000},"page":"H821-H828","source":"Crossref","is-referenced-by-count":28,"title":["Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells"],"prefix":"10.1152","volume":"297","author":[{"given":"C.","family":"Villeneuve","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Caudrillier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ordener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Pizzinat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Parini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Mialet-Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.02.020"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.528133"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2518fje"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.08.019"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308723101"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.8.1180"},{"key":"R7","unstructured":"Chandra M, Gupta V, Johri AK, Misra R, Kumar A, Gujrati V, Shanker K. 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Platelet derived serotonin drives the activation of rat cardiac fibroblasts by 5-HT2A receptors. 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