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FGF23/FGFR4-mediated left ventricular hypertrophy is reversible
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017), Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Portfolio, 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Biopsy
Science
030204 cardiovascular system & hematology
Fibroblast growth factor
Left ventricular hypertrophy
urologic and male genital diseases
Article
Muscle hypertrophy
Contractility
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Animals
Myocyte
Myocytes, Cardiac
Receptor, Fibroblast Growth Factor, Type 4
cardiovascular diseases
Mice, Knockout
Multidisciplinary
business.industry
Fibroblast growth factor receptor 4
medicine.disease
Myocardial Contraction
Diet
Rats
3. Good health
Fibroblast Growth Factors
Disease Models, Animal
Fibroblast Growth Factor-23
stomatognathic diseases
030104 developmental biology
Endocrinology
Fibroblast growth factor receptor
Cardiology
Medicine
Hypertrophy, Left Ventricular
business
Signal Transduction
Kidney disease
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....e7e2c1769e03ae58ebdbf7c1c9078571