{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Castillero E"],"funding":["NHLBI NIH HHS","NCI NIH HHS"],"pagination":["eadc9606"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9896655"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(677)"],"pubmed_abstract":["Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and <i>SERT</i> promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in <i>SERT</i><sup>-/-</sup> mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin recepto"],"journal":["Science translational medicine"],"pubmed_title":["Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation."],"pmcid":["PMC9896655"],"funding_grant_id":["R01 HL131872","P30 CA013696"],"pubmed_authors":["Nissim I","Pressly BB","Oyama MA","Ferrari G","Simpson MT","D'Angelo AM","Camillo C","Brown C","Krieger AM","Castillero E","Salvati E","Aghali A","Keeney SJ","Moreno V","Levy RJ","Grau JB","Rauova L","Kurade M","Shukla HJ","Stachelek SJ","Fitzpatrick E","Inamdar VV","Erwin WC"],"additional_accession":[]},"is_claimable":false,"name":"Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.","description":"Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and <i>SERT</i> promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in <i>SERT</i><sup>-/-</sup> mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin recepto","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-04-04T03:01:12.478Z","creation":"2025-04-04T03:01:12.478Z"},"accession":"S-EPMC9896655","cross_references":{"pubmed":["36599005"],"doi":["10.1126/scitranslmed.adc9606"]}}