Cited by 583Atrial Fibrillation Management and OutcomesCardiac Fibrosis and RemodelingCardiac electrophysiology and arrhythmias

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Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation

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Goette, Andreas, Staack, Thorsten, Röcken, Christoph, Arndt, Marco, Geller, J.Christoph, Huth, Christof, Ansorge, Siegfried, Klein, Helmut U, Lendeckel, Uwe·2000·Journal of the American College of Cardiology

DOI 10.1016/s0735-1097(00)00611-2

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Abstract

Objectives The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF).Background Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear.Methods Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or =6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques.Results Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis.Conclusions An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF.

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Authors: Goette, A., Staack, T., Röcken, C., Arndt, M., Geller, J. C., Huth, C., Ansorge, S., Klein, H. U., & Lendeckel, U.
Affiliations: University Hospital Magdeburg (DE)
Corresponding author: Goette, Andreas
ORCID: Goette, Andreas
Staack, Thorsten
Röcken, Christoph
Arndt, Marco
Geller, J.Christoph
Klein, Helmut U
Lendeckel, Uwe
Venue: Journal of the American College of Cardiology
Publisher: Elsevier BV
Published: 2000-05
Volume: 35
Issue: 6
Pages: 1669-1677
ISSN: 0735-1097 (ISSN-L)
DOI: 10.1016/s0735-1097(00)00611-2
OpenAlex: W2038843437
Cited by: 583
References: 47
Citations by year: 2026: 5 · 2025: 8 · 2024: 14 · 2023: 10 · 2022: 17 · 2021: 17 · 2020: 15 · 2019: 17 · 2018: 10 · 2017: 17 · 2016: 20 · 2015: 17 · 2014: 23 · 2013: 24 · 2012: 27
FWCI: 10.88
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4824 d)
Locations: Journal of the American College of Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords: atrial fibrillation, extracellular signal-regulated kinase, ERK1/ERK2, angiotensin-converting enzyme, atrial fibrosis, MEK1/2, interstitial cells, chronic atrial fibrillation, paroxysmal atrial fibrillation, ACE inhibitors, MAPK signaling
MeSH terms: Aged, Atrial Fibrillation, Endomyocardial Fibrosis, Female, Heart Atria, Humans, Peptidyl-Dipeptidase A, Male, Middle Aged, RNA, Messenger, Gene Expression Regulation, Enzymologic, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3

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Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation

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