{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:55:00Z","timestamp":1770886500595,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"Objectives<\/jats:title>Although critical in animal and human development and pathology, a measurement of the quantitative expression of 5-HTR serotonin receptors on animal or human valvular tissues has never been performed.<\/jats:p><\/jats:sec>Methods<\/jats:title>Quantification of the most frequent 5-HTRs reported as being present in human peripheral tissue was performed using radiolabeled agonists\/antagonists. A membrane protein extract from normal human valves (aortic\/mitral\/tricuspid and some pulmonary) and associated diseased left myocardium, all unusable in clinics, were obtained from the Homograft bank.<\/jats:p><\/jats:sec>Results<\/jats:title>We analyzed 5-HT1A<\/jats:sub>R\/5-HT1B\/D<\/jats:sub>R\/5-HT2A<\/jats:sub>R\/5-HT2B<\/jats:sub>R\/5-HT 2C<\/jats:sub>R\/5-HT4<\/jats:sub>R\/5-HT7<\/jats:sub>R from 28 hearts. We confirmed the presence of tissue and measured the quantitative content for respective proteins in femtomol\/mg of protein extracts: for 5-HT2A<\/jats:sub>R (35.9+\/\u22120.7), 5-HT2B<\/jats:sub>R (28.8+\/\u22121.3) but also a newly observed and robust expression for 5-HT4<\/jats:sub>R (38+\/\u22124.2). We identified one, 5-HT1A<\/jats:sub>Rs (4.9+\/\u22120.3), and the possible expression, but at a very low level, of previously reported 5-HT1B\/D<\/jats:sub>Rs (1.3+\/\u22120.5) as well as the new 5-HT7<\/jats:sub>Rs (3.5+\/0.1) and 5-HT2C<\/jats:sub>Rs (1.2+\/\u22120.1). Interestingly, by using univariate analysis, we were able to observe many correlations between the different 5-HTR levels of expression especially between 5-HT1A<\/jats:sub>R\/5-HT1B\/D<\/jats:sub>R and also between 5-HT4<\/jats:sub>R\/5-HT7<\/jats:sub>R, but none were observed between 5-HT2A<\/jats:sub>R and 5-HT2B<\/jats:sub>R. Using multivariate analyses for a specific 5-HTR level of expression, after adjustment for implantation sites and other 5-HTRs, we found that 5-HT1A<\/jats:sub>R was correlated with 5-HT1B\/D<\/jats:sub>R;5-HT4<\/jats:sub>R with 5-HT7<\/jats:sub>R and 5-HT1A<\/jats:sub>R;5-HT2B<\/jats:sub>R with 5-HT2A<\/jats:sub>R only. For 5-HT2<\/jats:sub>C, no correlation was observed.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>5-HT2A<\/jats:sub>R\/5-HT2B<\/jats:sub>R and 5-HT4<\/jats:sub>R were all observed to have a high and equal level of expression on human valves, but that of 5-HT1A<\/jats:sub>R was more limited. Since these non-5-HT2<\/jats:sub>Rs are coupled with different G-proteins, with specific signaling, theoretically they may control the main 5-HT2<\/jats:sub>R signaling (i.e., PLC\/DAG-PKC-ERK\/Ras\/Src signaling) involved in valvular fibrosis and degeneration.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.897657","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T07:11:49Z","timestamp":1666681909000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["First quantitative dosages: Strong correlations between non-5-HT2Rs serotonin receptors on normal human heart 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