ArticleJournal of molecular and cellular cardiology2018
Serotonin receptor 2B signaling with interstitial cell activation and leaflet remodeling in degenerative mitral regurgitation.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Drug-associated valvular heart diseases and serotonin-related pathways: a meta-analysis.Heart (British Cardiac Society) · 2019Pooled it
- The Serotonin 2B (5-HT2B) Receptor: A Narrative Review of Preclinical and Clinical Evidence on the Safety Considerations and Therapeutic Potential for the Treatment of Depression.Clinical pharmacology and therapeutics · 2026Review
- Specific serotonin receptor antagonist reduces murine calcific atherosclerosis.Atherosclerosis · 2026Article
- Serotonin transporter downregulation is associated with aortic stenosis, and early profibrotic remodeling is mitigated by pharmacological inhibition of HTR2B receptor.Frontiers in cardiovascular medicine · 2026Article
- Cardiology's best friend: Using naturally occurring disease in dogs to understand heart disease in humans.Journal of molecular and cellular cardiology plus · 2025Review
- Whole exome sequencing of 80 cases of sporadic mitral valve prolapse reveals novel disease-associated genes and variants in a Southern Chinese population.Genes & genomics · 2025Article
- Simulated Effects of Acute Left Ventricular Myocardial Infarction on Mitral Regurgitation in an Ovine Model.Journal of biomechanical engineering · 2024Article
- Mendelian randomization reveals interactions of the blood proteome and immunome in mitral valve prolapse.Communications medicine · 2024Article
- Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.Science translational medicine · 2023Article
- TGF-β phospho antibody array identifies altered SMAD2, PI3K/AKT/SMAD, and RAC signaling contribute to the pathogenesis of myxomatous mitral valve disease.Frontiers in veterinary science · 2023Article
- Editorial: Heart valve diseases: from molecular mechanisms to clinical implications.Frontiers in molecular medicine · 2023Article
- Bioinformatic analysis of potential biomarkers and mechanisms of immune infiltration in mitral regurgitation complicated by atrial fibrillation.Annals of translational medicine · 2022Article
- Connections for Matters of the Heart: Network Medicine in Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2022Review
- Telotristat ethyl reverses myxomatous changes in mice mitral valves.Frontiers in cardiovascular medicine · 2022Article
- First quantitative dosages: Strong correlations between non-5-HTFrontiers in cardiovascular medicine · 2022Article
- Update in carcinoid heart disease - the heart of the matter.Reviews in endocrine & metabolic disorders · 2021Review
- Targeting 5-HTCirculation · 2021Article
- Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Comparative transcriptomic profiling of myxomatous mitral valve disease in the cavalier King Charles spaniel.BMC veterinary research · 2020Article
- Disease Severity-Associated Gene Expression in Canine Myxomatous Mitral Valve Disease Is Dominated by TGFβ Signaling.Frontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 2 countries.
Funding
Abstract
aimsMitral valve interstitial cells (MVIC) play an important role in the pathogenesis of degenerative mitral regurgitation (MR) due to mitral valve prolapse (MVP). Numerous clinical studies have observed serotonin (5HT) dysregulation in cardiac valvulopathies; however, the impact of 5HT-mediated signaling on MVIC activation and leaflet remodeling in MVP have been investigated to a limited extent. Here we test the hypothesis that 5HT receptors (5HTRs) signaling contributes to MVP pathophysiology. METHODS AND
resultsDiseased human MV leaflets were obtained during cardiac surgery for MVP; normal MV leaflets were obtained from heart transplants. MV RNA was used for microarray analysis of MVP patients versus control, highlighting genes that indicate the involvement of 5HTR pathways and extracellular matrix remodeling in MVP. Human MV leaflets were also studied in vitro and ex vivo with biomechanical testing to assess remodeling in the presence of a 5HTR2B antagonist (LY272015). MVP leaflets from Cavalier King Charles Spaniels were used as a naturally acquired in vivo model of MVP. These canine MVP leaflets (N=5/group) showed 5HTR2B upregulation. This study also utilized CB57.1ML/6 mice in order to determine the effect of Angiotensin II infusion on MV remodeling. Histological analysis showed that MV thickening due to chronic Angiotensin II remodeling is mitigated by a 5HTR2B antagonist (LY272015) but not by 5HTR2A inhibitors.
conclusionIn humans, MVP is associated with an upregulation in 5HTR2B expression and increased 5HT receptor signaling in the leaflets. Antagonism of 5HTR2B mitigates MVIC activation in vitro and MV remodeling in vivo. These observations support the view that 5HTR signaling is involved not only in previously reported 5HT-related valvulopathies, but it is also involved in the pathological remodeling of MVP.
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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.