Fibroblast growth factor (FGF) 23 and FGF receptor 4 induced cardiac mitochondrial dysfunction as a new target in
Dieter Haffner1, Maren Leifheit-Nestler1
1Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany.
Insights
Fibroblast growth factor 23 (FGF23) promotes cardiovascular mortality in chronic kidney disease. FGF23-FGF receptor 4 signaling causes early cardiac mitochondrial dysfunction and metabolic remodeling before structural changes occur.
Area of Science:
- Nephrology
- Cardiology
- Molecular Biology
Background:
- Chronic kidney disease (CKD) is linked to high cardiovascular mortality.
- The phosphaturic hormone fibroblast growth factor 23 (FGF23) is implicated in CKD's cardiovascular complications.
- Elevated FGF23 contributes to left ventricular hypertrophy through FGF receptor 4 (FGFR4) activation.
Purpose of the Study:
- To investigate the role of FGF23-FGFR4 signaling in early cardiac complications of CKD.
- To explore FGF23's impact on cardiac mitochondrial function and metabolism.
Main Methods:
- Utilized bioengineered cardiobundles.
- Employed neonatal rat ventricular myocytes.
- Studied mice models with induced chronic kidney disease.
Main Results:
- Demonstrated FGF23-FGFR4 activation as a mechanism for cardiac mitochondrial dysfunction in CKD.
- Showed FGF23-FGFR4 signaling contributes to metabolic remodeling in the heart.
- Identified these cardiac changes occur before structural alterations in CKD.
Conclusions:
- FGF23-FGFR4 signaling is a key driver of early cardiac mitochondrial dysfunction and metabolic remodeling in CKD.
- These molecular and metabolic changes precede the development of structural cardiac abnormalities in CKD.
- Targeting FGF23-FGFR4 pathways may offer therapeutic strategies for CKD-associated cardiovascular disease.
Abstract:
Chronic kidney disease is associated with excessive cardiovascular mortality, which is promoted by the phosphaturic hormone fibroblast growth factor 23 (FGF23). Increased FGF23 levels result in left ventricular hypertrophy via activation of the FGF receptor 4 activation. Fuchs et al. now demonstrate, using bioengineered cardiobundles, neonatal rat ventricular myocytes, and mice with chronic kidney disease, that FGF23-FGF receptor 4 activation is a potential mechanism of cardiac mitochondrial dysfunction and metabolic remodeling as early complications of chronic kidney disease, preceding structural cardiac changes.
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