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
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引用次数: 0
Abstract
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.
期刊介绍:
Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed.
Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to):
DNA methylation
Nucleosome positioning and modification
Gene silencing
Imprinting
Nuclear reprogramming
Chromatin remodeling
Non-coding RNA
Non-histone chromosomal elements
Dosage compensation
Nuclear organization
Epigenetic therapy and diagnostics
Nutrition and environmental epigenetics
Cancer epigenetics
Neuroepigenetics