Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors
Fibrosis, cardiac remodelling, and inflammation are hallmarks of heart failure. To date, there is no available pharmacological cure for heart failure, but mechanical unloading by implantation of a left ventricular assist device (LVAD) can lead to improved cardiac function in a subset of patients. Th...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Epigenetics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15592294.2025.2506625 |
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| author | Rebekka Roth Margareta Häckh Tilman Schnick Carolin Rommel Christoph Koentges Heiko Bugger Claudia Domisch Michael R. Bristow Amrut V. Ambardekar Timothy A. McKinsey Ralf Gilsbach Lutz Hein Sebastian Preissl |
| author_facet | Rebekka Roth Margareta Häckh Tilman Schnick Carolin Rommel Christoph Koentges Heiko Bugger Claudia Domisch Michael R. Bristow Amrut V. Ambardekar Timothy A. McKinsey Ralf Gilsbach Lutz Hein Sebastian Preissl |
| author_sort | Rebekka Roth |
| collection | DOAJ |
| description | Fibrosis, cardiac remodelling, and inflammation are hallmarks of heart failure. To date, there is no available pharmacological cure for heart failure, but mechanical unloading by implantation of a left ventricular assist device (LVAD) can lead to improved cardiac function in a subset of patients. This study aimed to identify the transcriptional response of left ventricular (LV) cardiac myocytes to mechanical unloading in a mouse model of reversible LV pressure overload and in failing human hearts after LVAD implantation. We found that partial recovery of ventricular dysfunction, LV hypertrophy, and gene expression programmes occurred in mice under reversible transverse aortic constriction (rTAC). Gene expression analysis in cardiac myocytes identified a lasting repression of mitochondrial gene expression resulting in compromised fatty acid oxidation in the mouse model of reversible pressure overload and in human LV samples after LVAD therapy and a persistent upregulation of epigenetic and transcriptional regulators. These findings underpin that recovery from heart failure involves complex gene regulatory networks and that mitochondrial dysfunction remains a challenge even after mechanical unloading. Further studies are needed to investigate the functional role of these factors in reverse remodelling and recovery of failing hearts. |
| format | Article |
| id | doaj-art-d9636676ee984ce4bef2c72a6b881649 |
| institution | DOAJ |
| issn | 1559-2294 1559-2308 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj-art-d9636676ee984ce4bef2c72a6b8816492025-08-20T03:11:03ZengTaylor & Francis GroupEpigenetics1559-22941559-23082025-12-0120110.1080/15592294.2025.2506625Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factorsRebekka Roth0Margareta Häckh1Tilman Schnick2Carolin Rommel3Christoph Koentges4Heiko Bugger5Claudia Domisch6Michael R. Bristow7Amrut V. Ambardekar8Timothy A. McKinsey9Ralf Gilsbach10Lutz Hein11Sebastian Preissl12Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, GermanyDepartment of Cardiology and Angiology, Faculty of Medicine, University Heart Center, University of Freiburg, GermanyDepartment of Cardiology and Angiology, Faculty of Medicine, University Heart Center, University of Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, GermanyDepartment of Medicine, Division of Cardiology and Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Denver, CO, USADepartment of Medicine, Division of Cardiology and Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Denver, CO, USADepartment of Medicine, Division of Cardiology and Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Denver, CO, USAInstitute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, GermanyFibrosis, cardiac remodelling, and inflammation are hallmarks of heart failure. To date, there is no available pharmacological cure for heart failure, but mechanical unloading by implantation of a left ventricular assist device (LVAD) can lead to improved cardiac function in a subset of patients. This study aimed to identify the transcriptional response of left ventricular (LV) cardiac myocytes to mechanical unloading in a mouse model of reversible LV pressure overload and in failing human hearts after LVAD implantation. We found that partial recovery of ventricular dysfunction, LV hypertrophy, and gene expression programmes occurred in mice under reversible transverse aortic constriction (rTAC). Gene expression analysis in cardiac myocytes identified a lasting repression of mitochondrial gene expression resulting in compromised fatty acid oxidation in the mouse model of reversible pressure overload and in human LV samples after LVAD therapy and a persistent upregulation of epigenetic and transcriptional regulators. These findings underpin that recovery from heart failure involves complex gene regulatory networks and that mitochondrial dysfunction remains a challenge even after mechanical unloading. Further studies are needed to investigate the functional role of these factors in reverse remodelling and recovery of failing hearts.https://www.tandfonline.com/doi/10.1080/15592294.2025.2506625Heart failuremechanical unloadingreverse remodelingtranscriptomeepigeneticsmitochondria |
| spellingShingle | Rebekka Roth Margareta Häckh Tilman Schnick Carolin Rommel Christoph Koentges Heiko Bugger Claudia Domisch Michael R. Bristow Amrut V. Ambardekar Timothy A. McKinsey Ralf Gilsbach Lutz Hein Sebastian Preissl Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors Epigenetics Heart failure mechanical unloading reverse remodeling transcriptome epigenetics mitochondria |
| title | Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors |
| title_full | Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors |
| title_fullStr | Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors |
| title_full_unstemmed | Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors |
| title_short | Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors |
| title_sort | transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors |
| topic | Heart failure mechanical unloading reverse remodeling transcriptome epigenetics mitochondria |
| url | https://www.tandfonline.com/doi/10.1080/15592294.2025.2506625 |
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