Cardiac hypertrophy elevates serum levels of fibroblast growth factor 23

Kidney Int. 2018 Jul;94(1):60-71. doi: 10.1016/j.kint.2018.02.018. Epub 2018 May 8.


Several experimental studies have shown that fibroblast growth factor 23 (FGF23) induces left ventricular hypertrophy (LVH). However, the opposite directional relationship, namely a potential effect of LVH on FGF23, remains uncertain. Here we evaluated the effects of LVH on FGF23 using cardiomyocyte-specific calcineurin A transgenic mice. At six weeks, these mice showed severe LVH, with elevated levels of serum intact FGF23. FGF23 levels were elevated in cardiomyocytes, but not osteocytes, of the transgenic animals. Moreover, transverse aortic constriction also upregulated myocardial FGF23 expression in wild type mice. The promoter region of the FGF23 gene contains two putative nuclear factors of activated T cells (NFAT)-binding sites, with NFAT1 activating the promoter in a proximal NFAT-binding site dependent manner. Neither serum, urinary, or fractional excretion values of calcium and phosphate nor serum levels of 1,25(OH)2 vitamin D were different between wild type and transgenic mice. Moreover, the renal expression of FGF receptors and α-Klotho was comparable. However, plasma levels of antidiuretic hormone were significantly increased in the transgenic mice, and aquaporin-2 immunohistochemical staining was mainly positive in the apical membrane of the collecting duct, compared to a primarily cytoplasmic staining in wild type mice. Real-time PCR analyses of kidney CYP27B1 and CYP24A1 expression in wild type mice showed that exogenous antidiuretic hormone blocked FGF23's actions on these vitamin D activating or inactivating enzymes. Finally, the renal resistance of transgenic mice to FGF23 was partly overcome by tolvaptan. Thus, LVH in transgenic mice is associated with an increase in myocardial and serum intact FGF23, with the kidneys being protected against FGF23 excess by elevated antidiuretic hormone levels.

Keywords: FGF23; mineral metabolism; vasopressin.

MeSH terms

  • Animals
  • Calcineurin / genetics
  • Calcineurin / metabolism
  • Disease Models, Animal
  • Fibroblast Growth Factors / blood*
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Hypertrophy, Left Ventricular / blood*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocytes, Cardiac / metabolism
  • Osteocytes / metabolism
  • Vasopressins / blood


  • Vasopressins
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Calcineurin