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

• Published in: International journal of cardiology Vol. 166; no. 3; pp. 702 - 708
• Main Authors: Cao, Hailong, Li, Qingguo, Li, Mingna, OD, Røe, Wu, Zhong, Zhou, Qing, Cao, Bin, Chen, Baojun, Chen, Yijiang, Wang, Dongjin
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.07.2013; Elsevier
• Subjects: Adult; Atrial fibrillation; Atrial Fibrillation - metabolism; Atrial Fibrillation - pathology; Atrial remodeling; Atrial Remodeling - physiology; Biological and medical sciences; Biomarkers - metabolism; Cardiac dysrhythmias; Cardiology. Vascular system; Cardiovascular; Female; Heart; Humans; Male; Medical sciences; Middle Aged; Mitral Valve - metabolism; Mitral Valve - pathology; Mitral Valve - surgery; Osteoprotegerin; Osteoprotegerin - biosynthesis; RANK Ligand - biosynthesis; Receptor Activator of Nuclear Factor-kappa B - biosynthesis; Receptor activator of nuclear factor-κB; Receptor activator of nuclear factor-κB ligand; Atrial remodeling; Receptor activator of nuclear factor-κB ligand; Atrial fibrillation; Receptor activator of nuclear factor-κB; Osteoprotegerin; Human; Mitral valve; Arrhythmia; Ligand; Patient; Cardiovascular disease; Excitability disorder; Vascular remodeling; Activator; Heart disease; Transcription factor NFκB; Cardiology; Axis; Biological receptor
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2011.11.099

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.