title: Dysregulated atrial gene expression of osteoprotegerin/receptor activator of nuclear factor-κB (RANK)/RANK ligand axis in the development and progression of atrial fibrillation.
abstract: BACKGROUND
  Atrial structural remodeling is increasingly emphasized in initiation and perpetuation of atrial fibrillation (AF). Osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) axis, a key regulatory system in bone homeostasis, was recently linked to some cardiovascular disorders for its regulatory functions to myocardial remodeling. It was hypothesized that OPG/RANK/RANKL axis is involved in the development and progression of AF by regulating atrial structural remodeling.
  
  
  RESULTS
  Clinical data, and biopsies of right atrial appendage were collected from sex- and age-matched subjects: 24 persistent AF patients, 24 paroxysmal AF patients, 24 sinus rhythm patients undergoing isolated mitral valve surgery and 24 healthy heart donors. AF groups had higher atrial gene expression of OPG/RANK/RANKL axis and RANKL/OPG ratio, particularly in paroxysmal AF. This upregulated expression and activity were positively correlated with higher regulatory indicators of atrial structural remodeling as reflected by higher transcripts of tumor necrosis factor (TNF)-related apoptosis-inducing ligand, matrix metalloproteinase (MMP)-2 and MMP-9, pro-inflammatory factors TNF-α and interleukin-6, and higher ratios of MMP-9/tissue inhibitor of metalloproteinase (TIMP)-1 and MMP-2/TIMP-2 in AF.
  
  
  CONCLUSIONS
  The present findings suggest a potential role for known mediators of bone metabolism in the development and progression of AF and possibly represent new targets for therapeutic intervention in this disorder.
authors: Department of Thoracic and Cardiovascular Surgery, Nanjing University Medical School, Nanjing, Japan.
authors: Hailong
authors: H
authors: Cao
authors: Jian
authors: J
authors: Wang
authors: Lei
authors: L
authors: Xi
authors: Oluf Dimitri
authors: OD
authors: Røe
authors: Yijiang
authors: Y
authors: Chen
authors: Dongjin
authors: D
authors: Wang
mesh_terms: D000328:Adult; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis* / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9