Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation
Background Atrial fibrillation (AF) is the most common cardiac arrhythmia with a massive burden on global health. The prevalence of AF increases dramatically with age and can be up to 18% in patients older than 80 years. Telomeres, which are short, repeated DNA sequences at the end of chromosomes, a...
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Wiley
2025-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.037512 |
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| author | Kabita Pradhan Balram Neupane Paul Niehues Martin Kirschner Fabian Beier Chao‐Chung Kuo Erika Anneliese Hilbold Christian Bär Oana‐Maria Thoma Maximilian Waldner Margherita Vieri Tim H. Brümmendorf Vithurithra Tharmapalan Wolfgang Wagner Michael Kleines Mahdi Emrani Matthias Daniel Zink Andreas Napp Nikolaus Marx Michael Gramlich |
| author_facet | Kabita Pradhan Balram Neupane Paul Niehues Martin Kirschner Fabian Beier Chao‐Chung Kuo Erika Anneliese Hilbold Christian Bär Oana‐Maria Thoma Maximilian Waldner Margherita Vieri Tim H. Brümmendorf Vithurithra Tharmapalan Wolfgang Wagner Michael Kleines Mahdi Emrani Matthias Daniel Zink Andreas Napp Nikolaus Marx Michael Gramlich |
| author_sort | Kabita Pradhan |
| collection | DOAJ |
| description | Background Atrial fibrillation (AF) is the most common cardiac arrhythmia with a massive burden on global health. The prevalence of AF increases dramatically with age and can be up to 18% in patients older than 80 years. Telomeres, which are short, repeated DNA sequences at the end of chromosomes, are known to act as a biological aging marker. In this study, we investigated the relation of telomere shortening and AF in the context of atrial remodeling. Furthermore, we assessed changes in the gene expression profiles of patients with AF according to telomere length (TL) and left atrial fibrosis. Methods We included 72 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained to determine left atrial low voltage areas as a surrogate for atrial fibrosis. TL was quantified and correlated to low voltage areas. 3′ mRNA sequencing was performed for gene expression profiling. Clonal hematopoiesis of indeterminate potential was assessed by next generation sequencing. Telomerase reverse transcriptase knockout (Tert−/−) and telomerase RNA component knockout (Terc−/−) mice were used to investigate the mechanistic impact of telomere shortening on atrial remodeling. Results Patients with advanced left atrial fibrosis had shorter telomeres compared with patients with healthy left atria. Furthermore, there was a strong correlation between the extent of left atrial low voltage areas, TL, and outcome after catheter ablation of AF. 24 months after ablation, only 26.5% of patients with advanced fibrosis and short TL were in sinus rhythm compared with 62.5% of patients with no/low fibrosis and long TL. Gene expression profiles and clonal hematopoiesis of indeterminate potential frequency differed in patients with AF with short and long telomeres. Finally, atrial tissue of mouse models with shortened telomeres showed marked left atrial fibrosis and over‐expression of fibrosis‐related genes. Conclusions Telomere shortening is correlated with left atrial remodeling. Shorter telomeres are associated with a series of molecular events which could eventually lead to cardiac fibrosis and perpetuate AF. |
| format | Article |
| id | doaj-art-a110ace993c94bf6b98ded1caca386ee |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-a110ace993c94bf6b98ded1caca386ee2025-02-04T11:00:01ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-02-0114310.1161/JAHA.124.037512Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial FibrillationKabita Pradhan0Balram Neupane1Paul Niehues2Martin Kirschner3Fabian Beier4Chao‐Chung Kuo5Erika Anneliese Hilbold6Christian Bär7Oana‐Maria Thoma8Maximilian Waldner9Margherita Vieri10Tim H. Brümmendorf11Vithurithra Tharmapalan12Wolfgang Wagner13Michael Kleines14Mahdi Emrani15Matthias Daniel Zink16Andreas Napp17Nikolaus Marx18Michael Gramlich19Department of Cardiology University Hospital RWTH Aachen Aachen GermanyDepartment of Cardiology University Hospital RWTH Aachen Aachen GermanyDepartment of Cardiology University Hospital RWTH Aachen Aachen GermanyDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty University Hospital RWTH Aachen Aachen GermanyDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty University Hospital RWTH Aachen Aachen GermanyGenomics Facility, Interdisciplinary Center for Clinical Research (IZKF) University Hospital RWTH Aachen Aachen GermanyInstitute of Molecular and Translational Therapeutic Strategies (IMTTS) Hannover Medical School Hannover GermanyInstitute of Molecular and Translational Therapeutic Strategies (IMTTS) Hannover Medical School Hannover GermanyDepartment of Medicine 1 Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen GermanyDepartment of Medicine 1 Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen GermanyDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty University Hospital RWTH Aachen Aachen GermanyDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty University Hospital RWTH Aachen Aachen GermanyInstitute for Stem Cell Biology, Helmholtz Institute for Biomedical Engineering University Hospital RWTH Aachen Aachen GermanyCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD) Cologne GermanyDivision of Virology, Center of Laboratory Diagnostics University Hospital RWTH Aachen Aachen GermanyDepartment of Cardiology University Hospital RWTH Aachen Aachen GermanyDepartment of Cardiology University Hospital RWTH Aachen Aachen GermanyDepartment of Cardiology University Hospital RWTH Aachen Aachen GermanyDepartment of Cardiology University Hospital RWTH Aachen Aachen GermanyDepartment of Cardiology University Hospital RWTH Aachen Aachen GermanyBackground Atrial fibrillation (AF) is the most common cardiac arrhythmia with a massive burden on global health. The prevalence of AF increases dramatically with age and can be up to 18% in patients older than 80 years. Telomeres, which are short, repeated DNA sequences at the end of chromosomes, are known to act as a biological aging marker. In this study, we investigated the relation of telomere shortening and AF in the context of atrial remodeling. Furthermore, we assessed changes in the gene expression profiles of patients with AF according to telomere length (TL) and left atrial fibrosis. Methods We included 72 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained to determine left atrial low voltage areas as a surrogate for atrial fibrosis. TL was quantified and correlated to low voltage areas. 3′ mRNA sequencing was performed for gene expression profiling. Clonal hematopoiesis of indeterminate potential was assessed by next generation sequencing. Telomerase reverse transcriptase knockout (Tert−/−) and telomerase RNA component knockout (Terc−/−) mice were used to investigate the mechanistic impact of telomere shortening on atrial remodeling. Results Patients with advanced left atrial fibrosis had shorter telomeres compared with patients with healthy left atria. Furthermore, there was a strong correlation between the extent of left atrial low voltage areas, TL, and outcome after catheter ablation of AF. 24 months after ablation, only 26.5% of patients with advanced fibrosis and short TL were in sinus rhythm compared with 62.5% of patients with no/low fibrosis and long TL. Gene expression profiles and clonal hematopoiesis of indeterminate potential frequency differed in patients with AF with short and long telomeres. Finally, atrial tissue of mouse models with shortened telomeres showed marked left atrial fibrosis and over‐expression of fibrosis‐related genes. Conclusions Telomere shortening is correlated with left atrial remodeling. Shorter telomeres are associated with a series of molecular events which could eventually lead to cardiac fibrosis and perpetuate AF.https://www.ahajournals.org/doi/10.1161/JAHA.124.037512agingatrial fibrillationfibrosistelomere |
| spellingShingle | Kabita Pradhan Balram Neupane Paul Niehues Martin Kirschner Fabian Beier Chao‐Chung Kuo Erika Anneliese Hilbold Christian Bär Oana‐Maria Thoma Maximilian Waldner Margherita Vieri Tim H. Brümmendorf Vithurithra Tharmapalan Wolfgang Wagner Michael Kleines Mahdi Emrani Matthias Daniel Zink Andreas Napp Nikolaus Marx Michael Gramlich Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease aging atrial fibrillation fibrosis telomere |
| title | Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation |
| title_full | Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation |
| title_fullStr | Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation |
| title_full_unstemmed | Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation |
| title_short | Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation |
| title_sort | telomere length is associated with adverse atrial remodeling in patients with atrial fibrillation |
| topic | aging atrial fibrillation fibrosis telomere |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.037512 |
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