ArticleJournal of molecular and cellular cardiology2012
Down-regulation of the serotonin transporter in hyperreactive platelets counteracts the pro-thrombotic effect of serotonin.
Article in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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, 70 citations in OpenAlex.
- Discrepancy in Insulin Regulation between Gestational Diabetes Mellitus (GDM) Platelets and Placenta.The Journal of biological chemistry · 2016Trial
- GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Serotonin in Cardiovascular Disease: From Pathophysiological Insights to Clinical Utility.Diagnostics (Basel, Switzerland) · 2026Review
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Role of Serotonin, Membrane Transporter, and 5-HT2 Receptors in Pathogenesis of Atherosclerotic Plaque Formation in Immature Heterozygous Low-Density Lipoprotein-Receptor-Deficient Mice.International journal of molecular sciences · 2025Article
- Cross-talk between microbiota-gut-brain axis and blood pressure regulation.Clinical science (London, England : 1979) · 2025Review
- The Coordinated Changes in Platelet Glycan Patterns with Blood Serotonin and Exosomes.International journal of molecular sciences · 2024Review
- Membrane Transporter of Serotonin and Hypercholesterolemia in Children.International journal of molecular sciences · 2024Article
- Serotonin Signaling and the Hyperpermeable Endothelial Barrier in Sepsis: Clues to a Molecular Mechanism.Journal of community medicine & public health · 2024Article
- A Novel Antibody Targeting the Second Extracellular Loop of the Serotonin 5-HT2A Receptor Inhibits Platelet Function.International journal of molecular sciences · 2022Article
- Serotonin: a platelet hormone modulating cardiovascular disease.Journal of thrombosis and thrombolysis · 2021Review
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- Serotonin Transporter Deficiency is Associated with Dysbiosis and Changes in Metabolic Function of the Mouse Intestinal Microbiome.Scientific reports · 2019Article
- Frontiers of Serotonin Beyond the Brain.Pharmacological research · 2019Article
- Responses of Plasma Catecholamine, Serotonin, and the Platelet Serotonin Transporter to Cigarette Smoking.Frontiers in neuroscience · 2019Review
- Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR.Scientific reports · 2018Article
- Cigarette Smoking-Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets.Journal of the American Heart Association · 2017Article
- The Noncanonical Role of ULK/ATG1 in ER-to-Golgi Trafficking Is Essential for Cellular Homeostasis.Molecular cell · 2016Article
- Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability.Scientific reports · 2016Article
- Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice.PloS one · 2016Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
An elevated plasma concentration of serotonin ([5-HT]) is a common feature of cardiovascular disease often associated with enhanced platelet activation and thrombosis. Whether elevated in vivo plasma 5-HT per se represents an independent risk factor for platelet hyperreactivity or only is an epiphenomenon of cardiovascular disease is poorly understood. We examined in vitro and in vivo platelet function following a 24h elevation of plasma [5-HT] in mice. In vivo administration of 5-HT using osmotic minipumps increased plasma [5-HT] in treated mice compared to control mice instrumented with saline loaded pumps. 5-HT infusion did not increase systolic blood pressure, but markers of platelet activation including P-selectin and (PE)Jon/A staining were increased and these findings coincided with the enhanced aggregation of isolated platelets in response to type I fibrillar collagen. Tail bleeding times and the time to occlusion following chemical damage to the carotid artery were shortened in 5-HT-infused mice. 5-HT-infused mice were treated with paroxetine (Prx) to block 5-HT uptake via the serotonin transporter (SERT). Prx lowered platelet [5-HT] and attenuated platelet activation and aggregation. These results and our biochemical indices of enhanced 5-HT intracellular signaling in the platelets of 5-HT-infused mice reveal a mechanistic link between elevated plasma [5-HT], abnormal intracellular 5-HT signaling and accentuated platelet aggregation. Although a down-regulation of the serotonin transporter (SERT) on the platelet surface may counteract the pro-thrombotic influence of elevated plasma [5HT], this compensatory mechanism may fail to prevent the increased thrombotic risk caused by elevated plasma [5-HT].
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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.