Mapping DNA methylation to cardiac pathologies induced by beta-adrenergic stimulation in a large panel of mice
Heart failure (HF) is a major global health challenge, contributing to over 18 million deaths annually. While the roles of genetic and environmental factors are widely studied, the role of DNA methylation in HF pathogenesis is not fully understood. This study leverages the Hybrid Mouse Diversity Pan...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/15592294.2025.2524411 |
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| Summary: | Heart failure (HF) is a major global health challenge, contributing to over 18 million deaths annually. While the roles of genetic and environmental factors are widely studied, the role of DNA methylation in HF pathogenesis is not fully understood. This study leverages the Hybrid Mouse Diversity Panel (HMDP) to investigate the relationship between DNA methylation, gene expression, and HF phenotypes under isoproterenol-induced cardiac stress. Using reduced representational bisulfite sequencing, we analyzed DNA methylation profiles in the left ventricles of 90 HMDP strains. Epigenome-wide association studies identified 56 CpG loci linked to HF phenotypes, with 18 loci predicting HF progression. Key genes, including Prkag2, Anks1a, and Mospd3, were implicated through integration with gene expression and phenotypic data. In vitro validation confirmed the roles of Anks1aand Mospd3 in attenuating isoproterenol-induced hypertrophy. Additionally, treatment with the DNA methyltransferase inhibitor RG108 mitigated cardiac hypertrophy, preserved ejection fraction, and restored methylation-sensitive gene expression, underscoring the therapeutic potential of targeting DNA methylation in HF. This study highlights the interplay between DNA methylation, gene expression, and HF progression, offering new insights into its molecular underpinnings. The findings emphasize the role of epigenetic regulation in HF and suggest DNA methylation as a promising target for therapeutic intervention. |
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| ISSN: | 1559-2294 1559-2308 |