Details

Autor(en) / Beteiligte

• Lugenbiel, Patrick
• Govorov, Katharina
• Syren, Pascal
• Rahm, Ann-Kathrin
• Wieder, Teresa
• Wunsch, Maximilian
• Weiberg, Nadine
• Manolova, Emili
• Gramlich, Dominik
• Rivinius, Rasmus
• Finke, Daniel
• Lehmann, Lorenz H.
• Schweizer, Patrick A.
• Frank, Derk
• El Tahry, Fadwa A.
• Bruehl, Claus
• Heimberger, Tanja
• Sandke, Steffi
• Weis, Tanja
• Most, Patrick
• Schmack, Bastian
• Ruhparwar, Arjang
• Karck, Matthias
• Frey, Norbert
• Katus, Hugo A.
• Thomas, Dierk

Titel

Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes

Ist Teil von

• Basic research in cardiology, 2021-12, Vol.116 (1), p.13-13, Article 13

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Atrial fibrillation (AF) is associated with electrical remodeling, leading to cellular electrophysiological dysfunction and arrhythmia perpetuation. Emerging evidence suggests a key role for epigenetic mechanisms in the regulation of ion channel expression. Histone deacetylases (HDACs) control gene expression through deacetylation of histone proteins. We hypothesized that class I HDACs in complex with neuron-restrictive silencer factor (NRSF) determine atrial K + channel expression. AF was characterized by reduced atrial HDAC2 mRNA levels and upregulation of NRSF in humans and in a pig model, with regional differences between right and left atrium. In vitro studies revealed inverse regulation of Hdac2 and Nrsf in HL-1 atrial myocytes. A direct association of HDAC2 with active regulatory elements of cardiac K + channels was revealed by chromatin immunoprecipitation. Specific knock-down of Hdac2 and Nrsf induced alterations of K + channel expression. Hdac2 knock-down resulted in prolongation of action potential duration (APD) in neonatal rat cardiomyocytes, whereas inactivation of Nrsf induced APD shortening. Potential AF-related triggers were recapitulated by experimental tachypacing and mechanical stretch, respectively, and exerted differential effects on the expression of class I HDACs and K + channels in cardiomyocytes. In conclusion, HDAC2 and NRSF contribute to AF-associated remodeling of APD and K + channel expression in cardiomyocytes via direct interaction with regulatory chromatin regions. Specific modulation of these factors may provide a starting point for the development of more individualized treatment options for atrial fibrillation.