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Verfasst von:Schmidt, Constanze [VerfasserIn]   i
 Wiedmann, Felix Tobias [VerfasserIn]   i
 El-Battrawy, Ibrahim [VerfasserIn]   i
 Lan, Huan [VerfasserIn]   i
 Szabó, Gábor [VerfasserIn]   i
 Lang, Siegfried [VerfasserIn]   i
 Rapti, Kleopatra [VerfasserIn]   i
 Ratte, Antonius [VerfasserIn]   i
 Karck, Matthias [VerfasserIn]   i
 Akın, Ibrahim [VerfasserIn]   i
 Borggrefe, Martin [VerfasserIn]   i
 Zhou, Xiao-Bo [VerfasserIn]   i
 Katus, Hugo [VerfasserIn]   i
 Thomas, Dierk [VerfasserIn]   i
Titel:Genetic ablation of TASK-1 (tandem of P domains in a weak inward rectifying K+ channel-related acid-sensitive K+ channel-1) (K2P3.1) K+ channels suppresses atrial fibrillation and prevents electrical remodeling
Verf.angabe:Constanze Schmidt, MD, Felix Wiedmann, MD, Christoph Beyersdorf, BS, Zhi-han Zhao, MSc, Ibrahim El-Battrawy, MD, Huan Lan, MD, Gabor Szabo, MD, Xin Li, MSc, Siegfried Lang, PhD, Sevil Korkmaz-Icöz, MD, Kleopatra Rapti, PhD, Andreas Jungmann, PhD, Antonius Ratte, MD, Oliver J. Müller, MD, Matthias Karck, MD, Gunnar Seemann, PhD, Ibrahim Akin, MD, Martin Borggrefe, MD, Xiao-Bo Zhou, MD, Hugo A. Katus, MD, Dierk Thomas, MD
E-Jahr:2019
Jahr:September 13, 2019
Umfang:10 S.
Fussnoten:Gesehen am 05.12.2019
Titel Quelle:Enthalten in: Circulation. Arrhythmia and electrophysiology
Ort Quelle:Philadelphia, Pa. : Lippincott, Williams & Wilkins, 2008
Jahr Quelle:2019
Band/Heft Quelle:12(2019,1) Artikel-Nummer e007465, 10 Seiten
ISSN Quelle:1941-3084
Abstract:Background:Despite an increasing understanding of atrial fibrillation (AF) pathophysiology, translation into mechanism-based treatment options is lacking. In atrial cardiomyocytes of patients with chronic AF, expression, and function of tandem of P domains in a weak inward rectifying TASK-1 (K+ channel-related acid-sensitive K+ channel-1) (K2P3.1) atrial-specific 2-pore domain potassium channels is enhanced, resulting in action potential duration shortening. TASK-1 channel inhibition prevents action potential duration shortening to maintain values observed among sinus rhythm subjects. The present preclinical study used a porcine AF model to evaluate the antiarrhythmic efficacy of TASK-1 inhibition by adeno-associated viral anti-TASK-1-siRNA (small interfering RNA) gene transfer.Methods:AF was induced in domestic pigs by atrial burst stimulation via implanted pacemakers. Adeno-associated viral vectors carrying anti-TASK-1-siRNA were injected into both atria to suppress TASK-1 channel expression. After the 14-day follow-up period, porcine cardiomyocytes were isolated from right and left atrium, followed by electrophysiological and molecular characterization.Results:AF was associated with increased TASK-1 transcript, protein and ion current levels leading to shortened action potential duration in atrial cardiomyocytes compared to sinus rhythm controls, similar to previous findings in humans. Anti-TASK-1 adeno-associated viral application significantly reduced AF burden in comparison to untreated AF pigs. Antiarrhythmic effects of anti-TASK-1-siRNA were associated with reduction of TASK-1 currents and prolongation of action potential durations in atrial cardiomyocytes to sinus rhythm values.ConclusionsAdeno-associated viral-based anti-TASK-1 gene therapy suppressed AF and corrected cellular electrophysiological remodeling in a porcine model of AF. Suppression of AF through selective reduction of TASK-1 currents represents a new option for antiarrhythmic therapy.
DOI:doi:10.1161/CIRCEP.119.007465
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1161/CIRCEP.119.007465
 Verlag: https://www.ahajournals.org/doi/10.1161/CIRCEP.119.007465
 DOI: https://doi.org/10.1161/CIRCEP.119.007465
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1684390370
Verknüpfungen:→ Zeitschrift

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