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Article Dans Une Revue Frontiers in Cardiovascular Medicine Année : 2022

First quantitative dosages: Strong correlations between non-5-HT2Rs serotonin receptors on normal human heart valves

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Résumé

Objectives 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. Methods 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. Results We analyzed 5-HT 1A R/5-HT 1B/D R/5-HT 2A R/5-HT 2B R/5-HT 2C R/5-HT 4 R/5-HT 7 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-HT 2A R (35.9+/−0.7), 5-HT 2B R (28.8+/−1.3) but also a newly observed and robust expression for 5-HT 4 R (38+/−4.2). We identified one, 5-HT 1A Rs (4.9+/−0.3), and the possible expression, but at a very low level, of previously reported 5-HT 1B/D Rs (1.3+/−0.5) as well as the new 5-HT 7 Rs (3.5+/0.1) and 5-HT 2C Rs (1.2+/−0.1). Interestingly, by using univariate analysis, we were able to observe many correlations between the different 5-HTR levels of expression especially between 5-HT 1A R/5-HT 1B/D R and also between 5-HT 4 R/5-HT 7 R, but none were observed between 5-HT 2A R and 5-HT 2B 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-HT 1A R was correlated with 5-HT 1B/D R;5-HT 4 R with 5-HT 7 R and 5-HT 1A R;5-HT 2B R with 5-HT 2A R only. For 5-HT 2 C, no correlation was observed. Conclusion 5-HT 2A R/5-HT 2B R and 5-HT 4 R were all observed to have a high and equal level of expression on human valves, but that of 5-HT 1A R was more limited. Since these non-5-HT 2 Rs are coupled with different G-proteins, with specific signaling, theoretically they may control the main 5-HT 2 R signaling (i.e., PLC/DAG-PKC-ERK/Ras/Src signaling) involved in valvular fibrosis and degeneration.
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Dates et versions

hal-03867505 , version 1 (23-11-2022)

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Olivier Schussler, Luc Maroteaux, Ramadan Jashari, Pierre Falcoz, Marco Alifano, et al.. First quantitative dosages: Strong correlations between non-5-HT2Rs serotonin receptors on normal human heart valves. Frontiers in Cardiovascular Medicine, 2022, 9, pp.897657. ⟨10.3389/fcvm.2022.897657⟩. ⟨hal-03867505⟩
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