Direct hypertrophic effects of fibroblast growth factor 23 on cardiomyocytes

Abstract

Fibroblast growth factor 23 (FGF23) is a secreted, bone derived hormone that regulates vitamin D and phosphate metabolism. Recent clinical data shows a correlation between elevated levels of serum FGF23 in patients with chronic kidney disease (CKD) and cardiac disease. Therefore, we investigated the direct effects of a pathophysiological concentration of FGF23 on cardiomyocyte hypertrophy. Using flow cytometry we observed an 18% increase in HL‐1 cardiomyocyte cell size after 48 hour exposure to 900 pg/mL FGF23 (FSC; p<0.05; n=5). These hypertrophic effects on cells were verified in ventricular muscle tissue strips where treatment of FGF23 resulted in a 2 to5 fold increase in expression of common gene markers of cardiac hypertrophy (n=4–7; p<0.05) and elevated ERK1/2 phosphorylation (n=4; p<0.05). We also observed a 10% increase in total protein concentration which was blocked with an FGFR1 inhibitor (n=5–7; p<0.05). These data show that FGF23 has direct effects on cardiomyocyte cell size and may be an important bone‐heart crosstalk regulator of cardiac hypertrophy. This may be of particular importance with certain bone diseases and CKD where FGF23 levels are elevated. This work was supported by AHA SDG 11SDG5330016 (MJW) and NIH NIAMS 1RC2AR058962 (MJW and LFB).