Genetic Ablation of Fgf23 or Klotho Does not Modulate Experimental Heart Hypertrophy Induced by Pressure Overload

Sci Rep. 2017 Sep 12;7(1):11298. doi: 10.1038/s41598-017-10140-4.

Abstract

Left ventricular hypertrophy (LVH) ultimately leads to heart failure in conditions of increased cardiac pre- or afterload. The bone-derived phosphaturic and sodium-conserving hormone fibroblast growth factor-23 (FGF23) and its co-receptor Klotho have been implicated in the development of uremic LVH. Using transverse aortic constriction (TAC) in gene-targeted mouse models, we examine the role of Fgf23 and Klotho in cardiac hypertrophy and dysfunction induced by pressure overload. TAC profoundly increases serum intact Fgf23 due to increased cardiac and bony Fgf23 transcription and downregulation of Fgf23 cleavage. Aldosterone receptor blocker spironolactone normalizes serum intact Fgf23 levels after TAC by reducing bony Fgf23 transcription. Notably, genetic Fgf23 or Klotho deficiency does not influence TAC-induced hypertrophic remodelling, LV functional impairment, or LV fibrosis. Despite the profound, aldosterone-mediated increase in circulating intact Fgf23 after TAC, our data do not support an essential role of Fgf23 or Klotho in the pathophysiology of pressure overload-induced cardiac hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / pharmacology
  • Animals
  • Biomarkers
  • Blood Pressure
  • Cardiomegaly / diagnosis
  • Cardiomegaly / etiology*
  • Cardiomegaly / metabolism
  • Cardiomegaly / physiopathology*
  • Disease Models, Animal
  • Disease Susceptibility
  • Fibroblast Growth Factors / blood
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Fibrosis
  • Gene Expression Regulation
  • Gene Knockout Techniques*
  • Glucuronidase / genetics*
  • Glucuronidase / metabolism
  • Mice
  • Mice, Knockout
  • Signal Transduction / drug effects
  • Spironolactone / pharmacology

Substances

  • Biomarkers
  • Spironolactone
  • Aldosterone
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Glucuronidase
  • klotho protein