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.
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: Huitzilihuitl Saucedo-Orozco; Jesus Vargas-Barron; Ricardo Márquez-Velazco; Julio Iván Farjat-Pasos; Karla Susana Martinez-Zavala; Valentin Jiménez-Rojas; Sergio Andres Criales-Vera; Jose Antonio Arias-Godínez; Giovanni Fuentevilla-Alvarez; Veronica Guarner-Lans; Israel Perez-Torres; Gabriela Melendez-Ramirez; Tomas Efrain Sanchez Perez; Maria Elena Soto Journal: Open Heart Date: 2022-08
Authors: Brian Schwartz; Morten Schou; Frederick L Ruberg; Dane Rucker; Jihoon Choi; Omar Siddiqi; Kevin Monahan; Lars Køber; Gunnar Gislason; Christian Torp-Pedersen; Charlotte Andersson Journal: JACC CardioOncol Date: 2022-07-19