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Pastor-Arroyo, E.M.* ; Gehring, N.H.* ; Krudewig, C.* ; Costantino, S.* ; Bettoni, C.* ; Knöpfel, T.* ; Sabrautzki, S. ; Lorenz-Depiereux, B. ; Pastor, J.* ; Strom, T.M. ; Hrabě de Angelis, M. ; Camici, G.G.* ; Paneni, F.* ; Wagner, C.A.* ; Rubio-Aliaga, I.*

The elevation of circulating fibroblast growth factor 23 without kidney disease does not increase cardiovascular disease risk.

Kidney Int. 94, 49-59 (2018)
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High circulating fibroblast growth factor 23 (FGF23) levels are probably a major risk factor for cardiovascular disease in chronic kidney disease. FGF23 interacts with the receptor FGFR4 in cardiomyocytes inducing left ventricular hypertrophy. Moreover, in the liver FGF23 via FGFR4 increases the risk of inflammation which is also found in chronic kidney disease. In contrast, X-linked hypophosphatemia is characterized by high FGF23 circulating levels due to loss of function mutations of the phosphate-regulating gene with homologies to an endopeptidase on the X chromosome (PHEX), but is not characterized by high cardiovascular morbidity. Here we used a novel murine X-linked hypophosphatemia model, the PhexC733RMhda mouse line, bearing an amino acid substitution (p.Cys733Arg) to test whether high circulating FGF23 in the absence of renal injury would trigger cardiovascular disease. As X-linked hypophosphatemia patient mimics, these mice show high FGF23 levels, hypophosphatemia, normocalcemia, and low/normal vitamin D levels. Moreover, these mice show hyperparathyroidism and low circulating soluble alpha Klotho levels. At the age of 27 weeks we found no left ventricular hypertrophy and no alteration of cardiac function as assessed by echocardiography. These mice also showed no activation of the calcineurin/NFAT pathway in heart and liver and no tissue and systemic signs of inflammation. Importantly, blood pressure, glomerular filtration rate and urea clearance were similar between genotypes. Thus, the presence of high circulating FGF23 levels alone in the absence of renal impairment and normal/high phosphate levels is not sufficient to cause cardiovascular disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cardiovascular Disease ; Chronic Kidney Disease ; Fgf23 ; Phosphate; X-linked Hypophosphatemia; Left-ventricular Hypertrophy; Phex Gene; Cardiac-hypertrophy; Soluble Klotho; Vitamin-d; Rickets; Phosphate; Mice; Fgf23
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 0085-2538
e-ISSN 1523-1755
Journal Kidney International
Quellenangaben Volume: 94, Issue: 1, Pages: 49-59 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place 360 Park Ave South, New York, Ny 10010-1710 Usa
Reviewing status Peer reviewed
Institute(s) CF Comparative Medicine (AVM)
Institute of Experimental Genetics (IEG)
Institute of Human Genetics (IHG)
POF-Topic(s) 30202 - Environmental Health
30201 - Metabolic Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500900-001
G-500600-001
G-500700-001
G-500600-003
DOI 10.1016/j.kint.2018.02.017
WOS ID WOS:000437660400010
Scopus ID 85046754856
PubMed ID 29735309
Erfassungsdatum 2018-06-05
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