RATIONALE: Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder. OBJECTIVE: Here, we use single atrial myofibrils and fast solution switching techniques to directly investigate the impact of cAF on myofilament mechanical function eliminating changes induced by the arrhythmia in atrial myocytes membranes and extracellular components. Remodeling of sarcomere proteins potentially related to the observed mechanical changes is also investigated. METHODS AND RESULTS: Myofibrils were isolated from atrial samples of 15 patients in sinus rhythm and 16 patients with cAF. Active tension changes following fast increase and decrease in [Ca(2+)] and the sarcomere length-passive tension relation were determined in the 2 groups of myofibrils. Compared to sinus rhythm myofibrils, cAF myofibrils showed (1) a reduction in maximum tension and in the rates of tension activation and relaxation; (2) an increase in myofilament Ca(2+) sensitivity; (3) a reduction in myofibril passive tension. The slow beta-myosin heavy chain isoform and the more compliant titin isoform N2BA were up regulated in cAF myofibrils. Phosphorylation of multiple myofilament proteins was increased in cAF as compared to sinus rhythm atrial myocardium. CONCLUSIONS: Alterations in active and passive tension generation at the sarcomere level, explained by translational and post-translational changes of multiple myofilament proteins, are part of the contractile dysfunction of human cAF and may contribute to the self-perpetuation of the arrhythmia and the development of atrial dilatation.
RATIONALE: Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder. OBJECTIVE: Here, we use single atrial myofibrils and fast solution switching techniques to directly investigate the impact of cAF on myofilament mechanical function eliminating changes induced by the arrhythmia in atrial myocytes membranes and extracellular components. Remodeling of sarcomere proteins potentially related to the observed mechanical changes is also investigated. METHODS AND RESULTS: Myofibrils were isolated from atrial samples of 15 patients in sinus rhythm and 16 patients with cAF. Active tension changes following fast increase and decrease in [Ca(2+)] and the sarcomere length-passive tension relation were determined in the 2 groups of myofibrils. Compared to sinus rhythm myofibrils, cAF myofibrils showed (1) a reduction in maximum tension and in the rates of tension activation and relaxation; (2) an increase in myofilament Ca(2+) sensitivity; (3) a reduction in myofibril passive tension. The slow beta-myosin heavy chain isoform and the more compliant titin isoform N2BA were up regulated in cAF myofibrils. Phosphorylation of multiple myofilament proteins was increased in cAF as compared to sinus rhythm atrial myocardium. CONCLUSIONS: Alterations in active and passive tension generation at the sarcomere level, explained by translational and post-translational changes of multiple myofilament proteins, are part of the contractile dysfunction of humancAF and may contribute to the self-perpetuation of the arrhythmia and the development of atrial dilatation.
Authors: Sarah C W Stevens; Markus Velten; Dane J Youtz; Yvonne Clark; Runfeng Jing; Peter J Reiser; Sabahattin Bicer; Raymond D Devine; Donna O McCarthy; Loren E Wold Journal: J Mol Cell Cardiol Date: 2015-05-16 Impact factor: 5.000
Authors: Niels Voigt; Na Li; Qiongling Wang; Wei Wang; Andrew W Trafford; Issam Abu-Taha; Qiang Sun; Thomas Wieland; Ursula Ravens; Stanley Nattel; Xander H T Wehrens; Dobromir Dobrev Journal: Circulation Date: 2012-03-28 Impact factor: 29.690
Authors: Maura Greiser; Benoît-Gilles Kerfant; George S B Williams; Niels Voigt; Erik Harks; Katharine M Dibb; Anne Giese; Janos Meszaros; Sander Verheule; Ursula Ravens; Maurits A Allessie; James S Gammie; Jolanda van der Velden; W Jonathan Lederer; Dobromir Dobrev; Ulrich Schotten Journal: J Clin Invest Date: 2014-10-20 Impact factor: 14.808