FGF23/FGFR4-mediated left ventricular hypertrophy is reversible.
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Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed. Here, we report that FGF23-induced cardiac hypertrophy is reversible in vitro and in vivo upon removal of the hypertrophic stimulus. Specific blockade of FGFR4 attenuates established LVH in the 5/6 nephrectomy rat model of CKD. Since CKD mimics a form of accelerated cardiovascular aging, we also studied age-related cardiac remodeling. We show that aging mice lacking FGFR4 are protected from LVH. Finally, FGF23 increases cardiac contractility via FGFR4, while known effects of FGF23 on aortic relaxation do not require FGFR4. Taken together, our data highlight a role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function, and indicate that pharmacological interference with cardiac FGF23/FGFR4 signaling might protect from CKD- and age-related LVH.
Hypertrophy, Left Ventricular
Disease Models, Animal
Fibroblast Growth Factors
Receptor, Fibroblast Growth Factor, Type 4
Published Version (Please cite this version)10.1038/s41598-017-02068-6
Publication InfoGrabner, Alexander; Wolf, Myles; Schramm, Karla; Silswal, Neerupma; Hendrix, Matt; Yanucil, Christopher; ... Faul, Christian (2017). FGF23/FGFR4-mediated left ventricular hypertrophy is reversible. Scientific reports, 7(1). pp. 1993. 10.1038/s41598-017-02068-6. Retrieved from https://hdl.handle.net/10161/18484.
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Assistant Professor in Medicine
I am a medical doctor (MD) with more than 7 years of research experience studying cell biology and pathophysiology in the context of renal disease. The overall goal of my laboratory is to analyze molecular mechanisms that contribute to chronic kidney disease (CKD) and the cardiorenal syndrome. We are interested in characterizing novel signaling pathways that are involved in the development of cardiac remodeling and heart failure, inflammation and that lead to progression of rena
Charles Johnson, M.D. Professor of Medicine
The focus of my research is disordered mineral metabolism across the spectrum of chronic kidney disease, including dialysis, kidney transplantation and earlier stages.My research has been published in leading general medicine and subspecialty journals, including the New England Journal of Medicine, JAMA, the Journal of Clinical Investigation, Circulation, Cell Metabolism, Journal of the American Society of Nephrolog
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