2020
DOI: 10.1101/2020.03.10.985382
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Inhibition and down regulation of the serotonin transporter contribute to the progression of degenerative mitral regurgitation

Abstract: Aims: Heart valve disease attributed to serotonin (5HT) has been observed with 5HT-secreting carcinoid tumors and in association with medications, such as the diet drug, Dexfenfluoramine, a serotonin transporter (SLC6A4) inhibitor and 5HT receptor (HTR) 2B agonist. HTR2B signaling upregulates TGFβ-1 resulting in increased production of extracellular matrix proteins. SLC6A4 internalizes 5HT, limiting HTR signaling. Selective 5HT reuptake inhibitors (SSRI), widely used antidepressants, target SLC6A4, thus enhanc… Show more

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Cited by 1 publication
(6 citation statements)
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“…Another recent study, using also qPCR in patients ( n = 44) with MV prolapse, has shown no up-regulation of 5-HT 2A R, while 5-HT 2B R was even down-regulated: (−1.4x), 5-HT 2C R (−3.9x), 5-HT 1B R (−5.5x), 5-HT 1D R (−3.1), 5-HT 7 R (−3.2x), and SERT (−5.2x). In this study, TPH1 has been shown to be down-regulated (−2.3x) but 5-HT 1A R and 5-HT 4 R were not significantly changed ( 5 ) (see Figure 4 ). TGF-β2 was again increased (2.3x), especially BMP4 (+2.0x), but not BMP3 (−2.7x) or BMP5 (−4.9x).…”
Section: Discussionmentioning
confidence: 50%
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“…Another recent study, using also qPCR in patients ( n = 44) with MV prolapse, has shown no up-regulation of 5-HT 2A R, while 5-HT 2B R was even down-regulated: (−1.4x), 5-HT 2C R (−3.9x), 5-HT 1B R (−5.5x), 5-HT 1D R (−3.1), 5-HT 7 R (−3.2x), and SERT (−5.2x). In this study, TPH1 has been shown to be down-regulated (−2.3x) but 5-HT 1A R and 5-HT 4 R were not significantly changed ( 5 ) (see Figure 4 ). TGF-β2 was again increased (2.3x), especially BMP4 (+2.0x), but not BMP3 (−2.7x) or BMP5 (−4.9x).…”
Section: Discussionmentioning
confidence: 50%
“…TGF-β2 was again increased (2.3x), especially BMP4 (+2.0x), but not BMP3 (−2.7x) or BMP5 (−4.9x). The blockers of SERT in vitro increased the 5-HT 2B R on VIC ( 5 ).…”
Section: Discussionmentioning
confidence: 99%
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