Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model
Abstract Atrial remodeling is a major pathophysiological mechanism of atrial fibrillation (AF). Atrial remodeling progresses with aging and background diseases, including hypertension, heart failure, and AF itself. However, its mechanism of action and reversibility have not been completely elucidate...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85382-8 |
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| author | Keiko Abe Tetsuo Sasano Yurie Soejima Haruhisa Fukayama Shigeru Maeda Tetsushi Furukawa |
| author_facet | Keiko Abe Tetsuo Sasano Yurie Soejima Haruhisa Fukayama Shigeru Maeda Tetsushi Furukawa |
| author_sort | Keiko Abe |
| collection | DOAJ |
| description | Abstract Atrial remodeling is a major pathophysiological mechanism of atrial fibrillation (AF). Atrial remodeling progresses with aging and background diseases, including hypertension, heart failure, and AF itself. However, its mechanism of action and reversibility have not been completely elucidated. In this study, we investigated the involvement of DNA methylation in atrial remodeling. Mice underwent transverse aortic constriction (TAC) to generate a pressure overload model. After 14 days, the TAC-operated mice showed a significant increase in the atrium/body weight ratio and deposition of collagen fibers in the atria. A comprehensive analysis using RNA-sequencing (RNA-Seq) and methyl-CpG-binding domain sequencing (MBD-Seq) in the left atrial tissue identified Hif3a and Ifltd1 as showing increased DNA methylation in their promoter regions and decreased RNA expression. In addition, we created a transient pressure overload model by removing the aortic constriction 3 or 7 days after the initial TAC procedure (R3 or R7 groups). A reduction in RNA expression was achieved at R3 for Hif3a and at R7 for Ifltd1. Heterozygous Dnmt1 gene-targeting mice (Dnmt1 mut ) showed disappearance of the reduction in RNA expression and an increase in the atrium/body weight ratio. Altogether, DNA methylation contributed to at least part of atrial remodeling in the pressure overload mouse model. |
| format | Article |
| id | doaj-art-ade235c69eb64c20a50b0a15add0b8f1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-ade235c69eb64c20a50b0a15add0b8f12025-01-26T12:34:15ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85382-8Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine modelKeiko Abe0Tetsuo Sasano1Yurie Soejima2Haruhisa Fukayama3Shigeru Maeda4Tetsushi Furukawa5Department of Dental Anesthesiology and Orofacial Pain Management, Institute of Science TokyoDepartment of Cardiovascular Medicine, Institute of Science TokyoDepartment of Pathology and Anatomical Sciences, Institute of Science TokyoDepartment of Dental Anesthesiology and Orofacial Pain Management, Institute of Science TokyoDepartment of Dental Anesthesiology and Orofacial Pain Management, Institute of Science TokyoInstitute of Science TokyoAbstract Atrial remodeling is a major pathophysiological mechanism of atrial fibrillation (AF). Atrial remodeling progresses with aging and background diseases, including hypertension, heart failure, and AF itself. However, its mechanism of action and reversibility have not been completely elucidated. In this study, we investigated the involvement of DNA methylation in atrial remodeling. Mice underwent transverse aortic constriction (TAC) to generate a pressure overload model. After 14 days, the TAC-operated mice showed a significant increase in the atrium/body weight ratio and deposition of collagen fibers in the atria. A comprehensive analysis using RNA-sequencing (RNA-Seq) and methyl-CpG-binding domain sequencing (MBD-Seq) in the left atrial tissue identified Hif3a and Ifltd1 as showing increased DNA methylation in their promoter regions and decreased RNA expression. In addition, we created a transient pressure overload model by removing the aortic constriction 3 or 7 days after the initial TAC procedure (R3 or R7 groups). A reduction in RNA expression was achieved at R3 for Hif3a and at R7 for Ifltd1. Heterozygous Dnmt1 gene-targeting mice (Dnmt1 mut ) showed disappearance of the reduction in RNA expression and an increase in the atrium/body weight ratio. Altogether, DNA methylation contributed to at least part of atrial remodeling in the pressure overload mouse model.https://doi.org/10.1038/s41598-025-85382-8Atrial fibrillationAtrial remodelingReverse remodelingMethylationHif3aIfltd1 |
| spellingShingle | Keiko Abe Tetsuo Sasano Yurie Soejima Haruhisa Fukayama Shigeru Maeda Tetsushi Furukawa Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model Scientific Reports Atrial fibrillation Atrial remodeling Reverse remodeling Methylation Hif3a Ifltd1 |
| title | Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model |
| title_full | Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model |
| title_fullStr | Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model |
| title_full_unstemmed | Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model |
| title_short | Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model |
| title_sort | hypermethylation of hif3a and ifltd1 is associated with atrial remodeling in pressure overload murine model |
| topic | Atrial fibrillation Atrial remodeling Reverse remodeling Methylation Hif3a Ifltd1 |
| url | https://doi.org/10.1038/s41598-025-85382-8 |
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