Dysregulated Atrial Gene Expression of Osteoprotegerin/Receptor Activator of Nuclear Factor-.KAPPA.B (RANK)/RANK Ligand Axis in the Development and Progression of Atrial Fibrillation

• Cao Hailong

  Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School

• Wang Jian

  Department of Thoracic and Cardiovascular Surgery, Affiliated Yixing People's Hospital of Jiangsu University Medical School

• Xi Lei

  Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University

• Røe Oluf Dimitri

  Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University Department of Oncology, St Olavs Hospital, Trondheim University Hospital

• Chen Yijiang

  Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University

• Wang Dongjin

  Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School

抄録

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. Methods and 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. (Circ J 2011; 75: 2781-2788)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 75 (12), 2781-2788, 2011

  一般社団法人 日本循環器学会

キーワード

• Atrial fibrillation
• Atrial structural remodeling
• Osteoprotegerin
• Receptor activator of nuclear factor-κB
• Receptor activator of nuclear factor-κB ligand

詳細情報

• CRID: 1390282680079095040
• NII論文ID: 10030033161
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-11-0795
• COI: 1:CAS:528:DC%2BC38Xps1Gm
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 22001292
• Web Site: http://www.jstage.jst.go.jp/article/circj/75/12/75_CJ-11-0795/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2012170740
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可