Osteoprotegerin/RANK/RANKL axis and atrial remodeling in mitral valvular patients with atrial fibrillation

Int J Cardiol. 2013 Jul 1;166(3):702-8. doi: 10.1016/j.ijcard.2011.11.099. Epub 2011 Dec 15.


Background: Atrial remodeling is considered as the structural basis for the development and sustaining of atrial fibrillation (AF). Osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) axis, a key regulatory system in bone metabolism, was recently identified in some cardiovascular disorders for its regulation to myocardial remodeling. We hypothesized that the OPG/RANK/RANKL axis is involved in development and perpetuation of AF by regulating atrial remodeling.

Methods: Biopsies of right atrial appendage and clinical data were collected from sex- and age-matched 24 persistent AF, 24 paroxysmal AF, 24 sinus rhythm (SR) patients undergoing isolated mitral valve surgery and 24 healthy heart donors (normal controls).

Results: A significantly increasing gradient of atrial expression of OPG, RANKL, RANK and RANKL/OPG ratio was identified in normal controls, SR and AF groups. RANKL/OPG ratio was also found significantly higher in paroxysmal AF than persistent AF. Furthermore, atrial expression and activity of the axis was statistically correlated with collagen III/I levels and ratio and the degree of interstitial fibrosis reflected by collagen volume fraction in right atrial appendages.

Conclusions: The present findings suggest a potential role for known mediators of bone homeostasis in the pathogenesis of AF and possibly represent new targets for therapeutic intervention in AF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrial Fibrillation / metabolism*
  • Atrial Fibrillation / pathology
  • Atrial Remodeling / physiology*
  • Biomarkers / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitral Valve / metabolism*
  • Mitral Valve / pathology
  • Mitral Valve / surgery
  • Osteoprotegerin / biosynthesis*
  • RANK Ligand / biosynthesis*
  • Receptor Activator of Nuclear Factor-kappa B / biosynthesis*


  • Biomarkers
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFSF11 protein, human