The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia

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The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia. / Rommel, Carolin; Rösner, Stephan; Lother, Achim; Barg, Margareta; Schwaderer, Martin; Gilsbach, Ralf; Bömicke, Timo; Schnick, Tilman; Mayer, Sandra; Doll, Sophia; Hesse, Michael; Kretz, Oliver; Stiller, Brigitte; Neumann, Franz-Josef; Mann, Matthias; Krane, Markus; Fleischmann, Bernd K; Ravens, Ursula; Hein, Lutz.

In: Circulation Research, Vol. 123, No. 5, 2018, p. 550-563.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rommel, C, Rösner, S, Lother, A, Barg, M, Schwaderer, M, Gilsbach, R, Bömicke, T, Schnick, T, Mayer, S, Doll, S, Hesse, M, Kretz, O, Stiller, B, Neumann, F-J, Mann, M, Krane, M, Fleischmann, BK, Ravens, U & Hein, L 2018, 'The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia', Circulation Research, vol. 123, no. 5, pp. 550-563. https://doi.org/10.1161/CIRCRESAHA.118.313036

APA

Rommel, C., Rösner, S., Lother, A., Barg, M., Schwaderer, M., Gilsbach, R., Bömicke, T., Schnick, T., Mayer, S., Doll, S., Hesse, M., Kretz, O., Stiller, B., Neumann, F-J., Mann, M., Krane, M., Fleischmann, B. K., Ravens, U., & Hein, L. (2018). The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia. Circulation Research, 123(5), 550-563. https://doi.org/10.1161/CIRCRESAHA.118.313036

Vancouver

Rommel C, Rösner S, Lother A, Barg M, Schwaderer M, Gilsbach R et al. The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia. Circulation Research. 2018;123(5):550-563. https://doi.org/10.1161/CIRCRESAHA.118.313036

Author

Rommel, Carolin ; Rösner, Stephan ; Lother, Achim ; Barg, Margareta ; Schwaderer, Martin ; Gilsbach, Ralf ; Bömicke, Timo ; Schnick, Tilman ; Mayer, Sandra ; Doll, Sophia ; Hesse, Michael ; Kretz, Oliver ; Stiller, Brigitte ; Neumann, Franz-Josef ; Mann, Matthias ; Krane, Markus ; Fleischmann, Bernd K ; Ravens, Ursula ; Hein, Lutz. / The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia. In: Circulation Research. 2018 ; Vol. 123, No. 5. pp. 550-563.

Bibtex

@article{64f11a4cb8d148cab29c85aaa39c7f37,
title = "The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia",
abstract = " Rationale: Structural and electrophysiological remodeling of the atria are recognized consequences of sustained atrial arrhythmias, such as atrial fibrillation (AF). The identification of underlying key molecules and signaling pathways has been challenging due to the changing cell type composition during structural remodeling of the atria. Objective: Thus, the aims of our study were (1) to search for transcription factors and downstream target genes, which are involved in atrial structural remodeling, (2) to characterize the significance of the transcription factor ETV1 in atrial remodeling and arrhythmia and (3) to identify ETV1-dependent gene regulatory networks in atrial cardiac myocytes. Methods and Results: The transcription factor ETV1 was significantly upregulated in atrial tissue from patients with permanent AF. Mice with cardiac myocyte-specific overexpression of ETV1 under control of the myosin heavy chain promoter developed atrial dilatation, fibrosis, thrombosis and arrhythmia. Cardiac myocyte-specific ablation of ETV1 in mice did not alter cardiac structure and function at baseline. Treatment with Ang II for two weeks elicited atrial remodeling and fibrosis in control, but not in ETV1-deficient mice. To identify ETV1-regulated genes, cardiac myocytes were isolated and purified from mouse atrial tissue. Active cis-regulatory elements in mouse atrial cardiac myocytes were identified by chromatin accessibility (ATAC-seq) and the active chromatin modification H3K27ac (ChIP-seq). 178 genes regulated by Ang II in an ETV1-dependent manner were associated with active cis-regulatory elements containing ETV1 binding sites. Various genes involved in Ca2+ handling or gap junction formation (Ryr2, Jph2, Gja5), potassium channels (Kcnh2, Kcnk3) as well as genes implicated in AF (Tbx5) were part of this ETV1-driven gene regulatory network. The atrial ETV1-dependent transcriptome in mice showed a significant overlap with the human atrial proteome of patients with permanent AF. Conclusions: This study identifies ETV1 as an important component in the pathophysiology of atrial remodeling associated with atrial arrhythmias.",
author = "Carolin Rommel and Stephan R{\"o}sner and Achim Lother and Margareta Barg and Martin Schwaderer and Ralf Gilsbach and Timo B{\"o}micke and Tilman Schnick and Sandra Mayer and Sophia Doll and Michael Hesse and Oliver Kretz and Brigitte Stiller and Franz-Josef Neumann and Matthias Mann and Markus Krane and Fleischmann, {Bernd K} and Ursula Ravens and Lutz Hein",
year = "2018",
doi = "10.1161/CIRCRESAHA.118.313036",
language = "English",
volume = "123",
pages = "550--563",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams & Wilkins",
number = "5",

}

RIS

TY - JOUR

T1 - The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia

AU - Rommel, Carolin

AU - Rösner, Stephan

AU - Lother, Achim

AU - Barg, Margareta

AU - Schwaderer, Martin

AU - Gilsbach, Ralf

AU - Bömicke, Timo

AU - Schnick, Tilman

AU - Mayer, Sandra

AU - Doll, Sophia

AU - Hesse, Michael

AU - Kretz, Oliver

AU - Stiller, Brigitte

AU - Neumann, Franz-Josef

AU - Mann, Matthias

AU - Krane, Markus

AU - Fleischmann, Bernd K

AU - Ravens, Ursula

AU - Hein, Lutz

PY - 2018

Y1 - 2018

N2 - Rationale: Structural and electrophysiological remodeling of the atria are recognized consequences of sustained atrial arrhythmias, such as atrial fibrillation (AF). The identification of underlying key molecules and signaling pathways has been challenging due to the changing cell type composition during structural remodeling of the atria. Objective: Thus, the aims of our study were (1) to search for transcription factors and downstream target genes, which are involved in atrial structural remodeling, (2) to characterize the significance of the transcription factor ETV1 in atrial remodeling and arrhythmia and (3) to identify ETV1-dependent gene regulatory networks in atrial cardiac myocytes. Methods and Results: The transcription factor ETV1 was significantly upregulated in atrial tissue from patients with permanent AF. Mice with cardiac myocyte-specific overexpression of ETV1 under control of the myosin heavy chain promoter developed atrial dilatation, fibrosis, thrombosis and arrhythmia. Cardiac myocyte-specific ablation of ETV1 in mice did not alter cardiac structure and function at baseline. Treatment with Ang II for two weeks elicited atrial remodeling and fibrosis in control, but not in ETV1-deficient mice. To identify ETV1-regulated genes, cardiac myocytes were isolated and purified from mouse atrial tissue. Active cis-regulatory elements in mouse atrial cardiac myocytes were identified by chromatin accessibility (ATAC-seq) and the active chromatin modification H3K27ac (ChIP-seq). 178 genes regulated by Ang II in an ETV1-dependent manner were associated with active cis-regulatory elements containing ETV1 binding sites. Various genes involved in Ca2+ handling or gap junction formation (Ryr2, Jph2, Gja5), potassium channels (Kcnh2, Kcnk3) as well as genes implicated in AF (Tbx5) were part of this ETV1-driven gene regulatory network. The atrial ETV1-dependent transcriptome in mice showed a significant overlap with the human atrial proteome of patients with permanent AF. Conclusions: This study identifies ETV1 as an important component in the pathophysiology of atrial remodeling associated with atrial arrhythmias.

AB - Rationale: Structural and electrophysiological remodeling of the atria are recognized consequences of sustained atrial arrhythmias, such as atrial fibrillation (AF). The identification of underlying key molecules and signaling pathways has been challenging due to the changing cell type composition during structural remodeling of the atria. Objective: Thus, the aims of our study were (1) to search for transcription factors and downstream target genes, which are involved in atrial structural remodeling, (2) to characterize the significance of the transcription factor ETV1 in atrial remodeling and arrhythmia and (3) to identify ETV1-dependent gene regulatory networks in atrial cardiac myocytes. Methods and Results: The transcription factor ETV1 was significantly upregulated in atrial tissue from patients with permanent AF. Mice with cardiac myocyte-specific overexpression of ETV1 under control of the myosin heavy chain promoter developed atrial dilatation, fibrosis, thrombosis and arrhythmia. Cardiac myocyte-specific ablation of ETV1 in mice did not alter cardiac structure and function at baseline. Treatment with Ang II for two weeks elicited atrial remodeling and fibrosis in control, but not in ETV1-deficient mice. To identify ETV1-regulated genes, cardiac myocytes were isolated and purified from mouse atrial tissue. Active cis-regulatory elements in mouse atrial cardiac myocytes were identified by chromatin accessibility (ATAC-seq) and the active chromatin modification H3K27ac (ChIP-seq). 178 genes regulated by Ang II in an ETV1-dependent manner were associated with active cis-regulatory elements containing ETV1 binding sites. Various genes involved in Ca2+ handling or gap junction formation (Ryr2, Jph2, Gja5), potassium channels (Kcnh2, Kcnk3) as well as genes implicated in AF (Tbx5) were part of this ETV1-driven gene regulatory network. The atrial ETV1-dependent transcriptome in mice showed a significant overlap with the human atrial proteome of patients with permanent AF. Conclusions: This study identifies ETV1 as an important component in the pathophysiology of atrial remodeling associated with atrial arrhythmias.

U2 - 10.1161/CIRCRESAHA.118.313036

DO - 10.1161/CIRCRESAHA.118.313036

M3 - Journal article

C2 - 29930145

VL - 123

SP - 550

EP - 563

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 5

ER -

ID: 198718040