Cardiomyocytes produce their own fibroblast growth factor 23 during ischemic heart failure

Objectives: Fibroblast growth factor 23 (FGF23), a member of the fibroblast growth factor family, is released by osteoblasts and known to be responsible for the phosphate homeostasis. Furthermore FGF23 is an important indicator of early alterations in mineral metabolism and a predictor of chronic kidney disease progression. Recently it was reported that serum levels of FGF23 correlate with the degree of vascular pathology in patients. However it is unknown whether FGF23 is directly expressed in the heart. Recently we observed that isolated cultured cardiomyocytes (CM) are able to produce FGF23 in vitro, but in vivo data are missing.

Methods: For this purpose we studied heart explants of 10 patients suffering from ischemic end-stage heart failure (EF < 20%) and 2 controls. The role of ischemic stress in CM was analyzed in Bl6 wild-type mice three weeks after myocardial infarction (MI) induced by LAD ligation. FGF23 expression and its receptor (FGFR1c) were assessed by immunohistochemical and western blot analysis.

Results: FGF23 positive cells were localized isolated or in groups in the border zone of infarcted tissue. In patients with ischemic cardiomyopathy the number of FGF23 expressing CM was 14.8 fold increased in comparison to healthy controls (p < 0.001). MI in mice induced a 4.7 fold higher (p < 0.01) amount of FGF23 positive CM than in the sham operated group. We detected an increased expression of FGFR1c in infiltrating interstitial cells (most probably macrophages) surrounding CM after MI. FGFR1c cells were mainly restricted to infarcted tissue with increased FGF23 expression.

Conclusion: For the first time we demonstrated an increased activity of the FGF23 and its receptor FGFR1c after MI in the heart. FGF23 could be a promising diagnostic and prognostic biomarker in case of ischemic heart failure.