Article ; Online: Identification of DNA methylation biomarkers for evaluating cardiovascular disease risk from epigenome profiles altered by low-dose ionizing radiation.
2024 Volume 16, Issue 1, Page(s) 19
Abstract: Background: Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that ... ...
| Abstract | Background: Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is unclear. Because endothelial cells play crucial roles in cardiovascular health and disease, we aimed to investigate whether low-dose radiation could lead to differential DNA methylation patterns at the genomic level in endothelial cell (EC) lines. Methods: We screened for changes in DNA methylation patterns in primary human aortic (HAECs) and coronary artery endothelial cells following exposure to low-dose ionizing radiation. Using a subset of genes altered via DNA methylation by low-dose irradiation, we performed gene ontology (GO) analysis to predict the possible biological network mediating the effect of low-dose radiation. In addition, we performed comprehensive validation using methylation and gene expression analyses, and ChIP assay to identify useful biomarkers among candidate genes for use in detecting low-dose radiation exposure in human primary normal ECs. Results: Low-dose radiation is sufficient to induce global DNA methylation alterations in normal EC lines. GO analysis demonstrated that these hyper- or hypo-methylated genes were linked to diverse biological pathways. Our findings indicated a robust correlation between promoter hypermethylation and transcriptional downregulation of four genes (PGRMC1, UNC119B, RERE, and FNDC3B) in response to low-dose ionizing radiation in HAECs. Conclusions: Based on these findings, the identified genes can serve as potential DNA methylation biomarkers for the assessment of cardiovascular risk upon exposure to low-dose radiation. |
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| MeSH term(s) | Humans ; DNA Methylation ; Epigenome ; Endothelial Cells ; Cardiovascular Diseases/genetics ; Biomarkers ; Radiation, Ionizing ; Membrane Proteins/genetics ; Receptors, Progesterone/genetics |
| Chemical Substances | Biomarkers ; PGRMC1 protein, human ; Membrane Proteins ; Receptors, Progesterone |
| Language | English |
| Publishing date | 2024-02-01 |
| Publishing country | Germany |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2553921-8 |
| ISSN | 1868-7083 ; 1868-7075 |
| ISSN (online) | 1868-7083 |
| ISSN | 1868-7075 |
| DOI | 10.1186/s13148-024-01630-0 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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