title: Osteoprotegerin/RANK/RANKL axis and atrial remodeling in mitral valvular patients with atrial fibrillation.
abstract: 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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Cao
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Li
authors.forename: Mingna
authors.initials: M
authors.lastname: Li
authors.forename: Røe
authors.initials: R
authors.lastname: Od
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.forename: Baojun
authors.initials: B
authors.lastname: Chen
authors.forename: Yijiang
authors.initials: Y
authors.lastname: Chen
authors.forename: Dongjin
authors.initials: D
authors.lastname: Wang
mesh_terms: D000328:Adult; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000473:pathology; D064752:Atrial Remodeling / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D053244:Osteoprotegerin / Q000096:biosynthesis*; D053245:RANK Ligand / Q000096:biosynthesis*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis*
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human