ArticleThe American journal of pathology2002
Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells.
Article in The American journal of pathology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 103 citations in OpenAlex.
- Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.Science translational medicine · 2023Article
- Serotonin-A Driver of Progressive Heart Valve Disease.Frontiers in cardiovascular medicine · 2022Review
- Comparison of Serotonin-Regulated Calcific Processes in Aortic and Mitral Valvular Interstitial Cells.ACS omega · 2021Article
- Serotonin receptor type 2B activation augments TNF-α-induced matrix mineralization in murine valvular interstitial cells.Journal of cellular biochemistry · 2021Article
- Aortic Valve Regurgitation: Pathophysiology and Implications for Surgical Intervention in the Era of TAVR.Structural heart : the journal of the Heart Team · 2020Article
- The role of fibroblast growth factor 1 and 2 on the pathological behavior of valve interstitial cells in a three-dimensional mechanically-conditioned model.Journal of biological engineering · 2019Article
- Carcinoid syndrome: update on the pathophysiology and treatment.Clinics (Sao Paulo, Brazil) · 2018Review
- The Role of Serotonin during Skin Healing in Post-Thermal Injury.International journal of molecular sciences · 2018Article
- Serotonin receptor 2B signaling with interstitial cell activation and leaflet remodeling in degenerative mitral regurgitation.Journal of molecular and cellular cardiology · 2018Article
- The role of 5-HTBritish journal of pharmacology · 2017Article
- Cardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study.Cardiovascular toxicology · 2015Article
- Childhood dystonias.Current treatment options in neurology · 2015Article
- Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves.PloS one · 2012Article
- Sex-related differences in gene expression by porcine aortic valvular interstitial cells.PloS one · 2012Article
- Mitral valve disease in Marfan syndrome and related disorders.Journal of cardiovascular translational research · 2011Review
- Filamin-a-related myxomatous mitral valve dystrophy: genetic, echocardiographic and functional aspects.Journal of cardiovascular translational research · 2011Review
- Serotonin receptors and heart valve disease--it was meant 2B.Pharmacology & therapeutics · 2011Review
- Aortic valve cyclic stretch causes increased remodeling activity and enhanced serotonin receptor responsiveness.The Annals of thoracic surgery · 2011Article
- The use of lorcaserin in the management of obesity: a critical appraisal.Drug design, development and therapy · 2010Review
- Lorcaserin for the treatment of obesity.Drugs of today (Barcelona, Spain : 1998) · 2010Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Serotonin [5-hydroxytryptamine (5-HT)]-mediated cardiac valvular disease has been commonly observed in patients with carcinoid tumors. Previous research by others using reverse transcriptase-polymerase chain reaction demonstrated that aortic valve cells expressed predominantly 5-HT(2A/2B) receptors (5-HT(2A)R). Related investigations by our group using sheep aortic valve interstitial cell (SAVIC) cultures demonstrated that 5-HT both up-regulates transforming growth factor (TGF)-beta1 expression and activity, and also results in increased phospholipase C (PLC) activity. Thus, the present study investigated the hypothesis that the 5-HT signaling pathway in SAVICs involves 5-HT(2)Rs with associated G-protein signal transduction. The objectives were to functionally characterize in SAVIC cultures the native serotonin receptor subtypes using specific agonists and antagonists, and to delineate the serotonin-signaling pathway. 5-HT administration caused a marked stimulation of PLC activity. SAVIC studies of specific agents that target the 5-HT(2)R subtypes indicate that this response seemed to be mediated predominantly by 5-HT(2A)Rs. Furthermore, the sheep 5-HT(2A)R was identified by reverse transcriptase-polymerase chain reaction with sequence confirmation including comparisons to pig and human 5-HT(2A)R. Extracellular signal-regulated kinase (Erk 1/2) is a signaling molecule downstream from the 5-HT(2A)R. Both a protein kinase C inhibitor, GF109203X, and a Src inhibitor, PP1, attenuated 5-HT-stimulated Erk 1/2 activation. However, a 5-HT(2A)R antagonist, MDL 100907, inhibited 5-HT up-regulation of PLC and TGF-beta1, while having far less pronounced effects on Erk 1/2. In conclusion, these studies of the signal transduction activity of SAVICs in response to 5-HT have demonstrated that the 5-HT(2A)Rs are the most functionally active of the 5-HT(2)Rs in this cell type. Furthermore, 5-HT(2A)Rs are also involved in 5-HT up-regulation of active TGF-beta. 5-HT also mediated strong Erk 1/2 signaling via the MAP-kinase pathway, which was only in part because of 5-HT(2A)R activity. Thus, major 5-HT Erk 1/2 signaling beyond that controlled by 5-HT(2)Rs must involve other serotonin receptor types and/or secondary signaling events.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.