Dysregulated atrial gene expression of osteoprotegerin/receptor activator of nuclear factor-κB (RANK)/RANK ligand axis in the development and progression of atrial fibrillation

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 d...

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Published in:Circulation journal : official journal of the Japanese Circulation Society Vol. 75; no. 12; p. 2781
Main Authors: Cao, Hailong, Wang, Jian, Xi, Lei, Røe, Oluf Dimitri, Chen, Yijiang, Wang, Dongjin
Format: Journal Article
Language:English
Published: Japan 2011
Subjects:
Adult
Atrial Fibrillation - genetics
Atrial Fibrillation - metabolism
Atrial Fibrillation - therapy
Disease Progression
Female
Gene Expression Regulation
Heart Atria - metabolism
Humans
Interleukin-6 - biosynthesis
Interleukin-6 - genetics
Male
Matrix Metalloproteinase 2 - biosynthesis
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 9 - biosynthesis
Matrix Metalloproteinase 9 - genetics
Middle Aged
Osteoprotegerin - biosynthesis
Osteoprotegerin - genetics
RANK Ligand - biosynthesis
RANK Ligand - genetics
Receptor Activator of Nuclear Factor-kappa B - biosynthesis
Receptor Activator of Nuclear Factor-kappa B - genetics
Tissue Inhibitor of Metalloproteinase-1 - biosynthesis
Tissue Inhibitor of Metalloproteinase-1 - genetics
Tissue Inhibitor of Metalloproteinase-2 - biosynthesis
Tissue Inhibitor of Metalloproteinase-2 - genetics
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - genetics
ISSN:1347-4820, 1347-4820
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Summary: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. 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. 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.
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ISSN:1347-4820
1347-4820
DOI:10.1253/circj.CJ-11-0795