Arterial klotho expression and FGF23 effects on vascular calcification and function

PLoS One. 2013;8(4):e60658. doi: 10.1371/journal.pone.0060658. Epub 2013 Apr 5.

Abstract

Recent studies support a role for FGF23 and its co-receptor Klotho in cardiovascular pathology, yet the underlying mechanisms remain largely elusive. Herein, we analyzed the expression of Klotho in mouse arteries and generated a novel mouse model harboring a vascular smooth muscle cell specific deletion of Klotho (Sm22-KL(-/-) ). Arterial Klotho expression was detected at very low levels with quantitative real-time PCR; Klotho protein levels were undetectable by immunohistochemistry and Western blot. There was no difference in arterial Klotho between Sm22-KL(-/-) and wild-type mice, as well as no changes in serum markers of mineral metabolism. Intravenous delivery of FGF23 elicited a rise in renal (0.005; p<0.01) but not arterial Egr-1 expression, a marker of Klotho-dependent FGF23 signaling. Further, the impact of FGF23 on vascular calcification and endothelial response was evaluated in bovine vascular smooth muscle cells (bVSMC) and in a murine ex vivo model of endothelial function, respectively. FGF23 treatment (0.125-2 ng/mL) did not modify calcification in bVSMCs or dilatory, contractile and structural properties in mice arterial specimen ex vivo. Collectively, these results demonstrate that FGF23-Klotho signaling is absent in mouse arteries and that the vascular response was unaffected by FGF23 treatment. Thus, our data do not support Klotho-mediated FGF23 effects in the vasculature although confirmative studies in humans are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / drug effects*
  • Arteries / metabolism*
  • Arteries / pathology
  • Arteries / physiopathology
  • Calcinosis / genetics
  • Calcinosis / metabolism*
  • Cattle
  • Early Growth Response Protein 1 / genetics
  • Female
  • Fibroblast Growth Factors / pharmacology*
  • Gene Deletion
  • Gene Expression Regulation / drug effects*
  • Glucuronidase / deficiency
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Male
  • Mice
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Phenotype
  • Time Factors

Substances

  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Glucuronidase
  • klotho protein