Fibroblast growth factor 23 (FGF23) induces ventricular arrhythmias and prolongs QTc interval in mice in an FGF receptor 4-dependent manner
Jonah Graves, Julian Vallejo, Chelsea S. Hamill, Derek Wang, Rohan Ahuja, Shaan Patel, Christian Faul, Michael Wacker
Abstract
Here we provide direct evidence that fibroblast growth factor 23 (FGF23), a phosphaturic hormone elevated in chronic kidney disease, is proarrhythmic. FGF23 acutely triggered ventricular arrhythmias and prolonged corrected QT interval (QTc) in isolated mouse hearts and in vivo. FGF23 also increased Ca 2+ levels in ventricular muscle tissue. Blockade of the FGF receptor 4 signaling pathway using a monoclonal antibody ameliorated ventricular arrhythmias, QTc prolongation, and elevated ventricular Ca 2+ induced by FGF23, and may represent a potential therapeutic target in chronic kidney disease.
Topics & Concepts
QT intervalFibroblast growth factor 23Fibroblast growth factorInternal medicineEndocrinologyMedicineBlockadeKidney diseaseReceptorKidneyCardiologyCalciumParathyroid hormoneParathyroid Disorders and TreatmentsFibroblast Growth Factor ResearchMagnesium in Health and Disease