ArticlePloS one2016
Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: Analysis of an ongoing long-term open-label safety extension study.Epilepsia · 2020Trial
- Estrogen and Cyp1b1 Regulate Pparγ in Pulmonary Hypertension Through a Ubiquitin-Dependent Mechanism.Pulmonary circulation · 2025Article
- Potent and Selective Human 5-HTJournal of medicinal chemistry · 2024Article
- Progression of pulmonary arterial hypertension: A study in model.Open veterinary journal · 2024Article
- Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.Neuro-oncology · 2024Article
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Novel Tryptophan Hydroxylase Inhibitor TPT-001 Reverses PAH, Vascular Remodeling, and Proliferative-Proinflammatory Gene Expression.JACC. Basic to translational science · 2024Article
- Development of a Peripherally Restricted 5-HTJACC. Basic to translational science · 2023Article
- 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery.Journal of medicinal chemistry · 2023Review
- Identification of Potent, Selective, and Peripherally Restricted Serotonin Receptor 2B Antagonists from a High-Throughput Screen.Assay and drug development technologies · 2023Article
- Review
- The occurrence and risk factors of bradycardia after the Maze procedure in patients with atrial fibrillation and tricuspid regurgitation.Journal of cardiothoracic surgery · 2021Article
- Targeting 5-HTCirculation · 2021Article
- Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Pathological Insight into 5-HTInternational journal of molecular sciences · 2020Review
- Target identification among known drugs by deep learning from heterogeneous networks.Chemical science · 2020Article
- Bone Marrow-Derived Proangiogenic Cells Mediate Pulmonary Arteriole Stiffening via Serotonin 2B Receptor Dependent Mechanism.Circulation research · 2018Article
- GPCRs in pulmonary arterial hypertension: tipping the balance.British journal of pharmacology · 2018Review
- Interaction of hepatic stellate cells with neutrophils and macrophages in the liver following oncogenic kras activation in transgenic zebrafish.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice.
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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 Socratic graph.