ArticleBritish journal of pharmacology2014
The contribution of VEGF signalling to fostamatinib-induced blood pressure elevation.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia: Phase 2, multicenter, open-label study.American journal of hematology · 2022Trial
- Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials.American journal of hematology · 2018Trial
- Studying the Vascular Tone of Mouse Aortic Rings in a Standard Wire Myograph.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A Pan-Cancer Analysis of Natriuretic Peptide Receptor 3 (NPR3) with Clinical Cohort and in vitro Validation.Journal of inflammation research · 2025Article
- Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19.Life science alliance · 2023Article
- Clinical Pharmacokinetics and Pharmacodynamics of Fostamatinib and Its Active Moiety R406.Clinical pharmacokinetics · 2022Review
- In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma.International journal of general medicine · 2022Article
- Eco-Friendly UPLC-MS/MS Method for Determination of a Fostamatinib Metabolite, Tamatinib, in Plasma: Pharmacokinetic Application in Rats.Molecules (Basel, Switzerland) · 2021Article
- Review
- Article
- The prognostic significance of inflammation-based scores in patients with ampullary carcinoma after pancreaticoduodenectomy.BMC cancer · 2020Article
- Role of the Spleen Tyrosine Kinase Pathway in Driving Inflammation in IgA Nephropathy.Seminars in nephrology · 2018Review
- Targeting the B cell receptor pathway in non-Hodgkin lymphoma.Expert opinion on investigational drugs · 2018Review
- Quantifying the relationship between inhibition of VEGF receptor 2, drug-induced blood pressure elevation and hypertension.British journal of pharmacology · 2018Article
- Fostamatinib in chronic immune thrombocytopenia: a profile of its use in the USA.Drugs & therapy perspectives : for rational drug selection and use · 2018Article
- Syk inhibitors in clinical development for hematological malignancies.Journal of hematology & oncology · 2017Review
- Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2017Review
- A Novel Triazolopyridine-Based Spleen Tyrosine Kinase Inhibitor That Arrests Joint Inflammation.PloS one · 2016Article
- Prevention of fostamatinib-induced blood pressure elevation by antihypertensive agents.Pharmacology research & perspectives · 2015Article
- In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib.Pharmacology research & perspectives · 2015Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeFostamatinib is an inhibitor of spleen tyrosine kinase (TK). In patients, fostamatinib treatment was associated with increased BP. Some TK inhibitors cause BP elevation, by inhibiting the VEGF receptor 2 (VEGFR2). Here, we have assessed the mechanistic link between fostamatinib-induced BP elevation and inhibition of VEGF signalling. EXPERIMENTAL APPROACH: We used conscious rats with automated blood sampling and radio telemetry and anaesthetized rats to measure cardiovascular changes. Rat isolated aorta and isolated hearts, and human resistance vessels in vitro were also used. NO production by human microvascular endothelial cells was measured with the NO-dependent probe, DAF-FM and VEGFR2 phosphorylation was determined in mouse lung, ex vivo. KEY
resultsIn conscious rats, fostamatinib dose-dependently increased BP. The time course of the BP effect correlated closely with the plasma concentrations of R406 (the active metabolite of fostamatinib). In anaesthetized rats, infusion of R406 increased BP and decreased femoral arterial conductance. Endothelial function was unaffected, as infusion of R406 did not inhibit hyperaemia- or ACh-induced vasodilatation in rats. R406 did not affect contraction of isolated blood vessels. R406 inhibited VEGF-stimulated NO production from human endothelial cells in vitro, and treatment with R406 inhibited VEGFR2 phosphorylation in vivo. R406 inhibited VEGF-induced hypotension in anaesthetized rats. CONCLUSIONS AND IMPLICATIONS: Increased vascular resistance, secondary to reduced VEGF-induced NO release from endothelium, may contribute to BP increases observed with fostamatanib. This is consistent with the elevated BP induced by other drugs inhibiting VEGF signalling, although the contribution of other mechanisms cannot be excluded.
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