Generate QR code
Open Access
Subscription Access
DNA methylation patterns in the long noncoding RNA NR2F1-AS1 gene region in ascending aortic aneurysm and atherosclerosis.
https://doi.org/10.25557/2073-7998.2025.12.74-79
Abstract
The contradictory findings regarding the comorbidity of thoracic aortic aneurysm and atherosclerosis underscore the need to identify shared and distinct molecular genetic factors underlying the relationship between these pathologies. Particular interest lies in investigating epigenetic modifications, specifically DNA methylation, in patients with concurrent thoracic aortic aneurysm and atherosclerosis. This study aimed to identify differentially methylated genes involved in both isolated and atherosclerosis-comorbid aortic pathology across aortic tissue, blood, and skin samples from patients with non-syndromic forms of thoracic aortic aneurysm. Differential methylation patterns of the non-coding RNA gene NR2F1-AS1 were identified between isolated and comorbid forms of aortic aneurysm and atherosclerosis: hypomethylation was observed in the dilated aortic region and atherosclerotic plaques of thoracic aortic aneurysm patients, whereas hypermethylation was detected in atherosclerotic plaques from patients with atherosclerosis without aneurysm. The results demonstrate bidirectional alterations in methylation levels within the non-coding RNA gene NR2F1-AS1 in both thoracic aortic aneurysm and aortic atherosclerosis, highlighting the significant role of non-coding RNAs in the pathogenesis of these conditions.
Supporting agencies: The work is supported by the grant of the Russian Science Foundation No. 22-25-00701.
About the Authors
S. A. Shipulina
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences
Россия
Россия
I. A. Goncharova
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences
Россия
Россия
A. A. Zarubin
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences
Россия
Россия
D. S. Panfilov
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Россия
Россия
B. N. Kozlov
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Россия
Россия
M. S. Nazarenko
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences
Россия
Россия
References
1. Huhta A., Paavonen T., Mennander A., et al. Interplay of atherosclerosis and medial degeneration in human ascending aorta. Cardiovasc Pathol. 2025; 74: 107702. doi: 10.1016/j.carpath.2024.107702.
2. Achneck H., Modi B., Shaw C., et al. Ascending thoracic aneurysms are associated with decreased systemic atherosclerosis. Chest. 2005;128(3):1580-6. doi:10.1378/chest.128.3.1580.
3. Curtis A., Smith T., Ziganshin B.A., et al. Ascending Aortic Proaneurysmal Genetic Mutations with Antiatherogenic Effects. Int J Angiol. 2015;24(3):189-97. doi:10.1055/s-0035-1556075.
4. Waldron C., Zafar M.A., Ziganshin B.A., et al. Evidence Accumulates: Patients with Ascending Aneurysms Are Strongly Protected from Atherosclerotic Disease. Int J Mol Sci. 2023;24(21):15640. doi:10.3390/ijms242115640.
5. Doppler C., Messner B., Mimler T., et al. Noncanonical atherosclerosis as the driving force in tricuspid aortic valve associated aneurysms A trace collection. J Lipid Res. 2023;64(3):100338. doi:10.1016/j.jlr.2023.100338.
6. Renard M., Francis C., Ghosh R., et al. Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection. J Am Coll Cardiol. 2018;72(6):605-15. doi:10.1016/j.jacc.2018.04.089.
7. Pinard A., Jones G.T., Milewicz D.M. Genetics of Thoracic and Abdominal Aortic Diseases. Circ Res. 2019;124(4):588-606. doi:10.1161/CIRCRESAHA.118.312436.
8. Zaina S., Heyn H., Carmona F.J., et al. DNA Methylation Map of Human Atherosclerosis. Circ Cardiovasc Genet. 2014;7(5):692-700. doi:10.1161/CIRCGENETICS.113.000441.
9. Lacey M., Baribault C., Ehrlich K.C., et al. Atherosclerosis associated differentially methylated regions can reflect the disease phenotype and are often at enhancers. Atherosclerosis. 2019;280:183 91. doi:10.1016/j.atherosclerosis.2018.11.031.
10. Shah A.A., Gregory S.G., Krupp D., et al. Epigenetic profiling identifies novel genes for ascending aortic aneurysm formation with bicuspid aortic valves. Heart Surg Forum. 2015;18(4):E134-9. doi:10.1532/hsf.1247.
11. Pan S., Lai H., Shen Y., et al. DNA methylome analysis reveals distinct epigenetic patterns of ascending aortic dissection and bicuspid aortic valve. Cardiovasc Res. 2017;113(6):692-704. doi:10.1093/cvr/cvx050.
12. Chen Y., Xu X., Chen Z., et al. DNA methylation alternation in Stanford A acute aortic dissection. BMC Cardiovasc Disord. 2022;22(1):455. doi:10.1186/s12872-022-02882-5.
13. Yao Q., Zhang X., Chen Y., et al. Long non-coding RNA NR2F1 AS1: an increasingly significant LncRNA in human cancers. J Physiol Biochem. 2025 Aug 19. doi:10.1007/s13105-025-01119-1. [Epub ahead of print]
14. Lim Y.H., Ryu J., Kook H., et al. Identification of Long Noncoding RNAs Involved in Differentiation and Survival of Vascular Smooth Muscle Cells. Mol Ther Nucleic Acids. 2020;22:209-221. doi:10.1016/j.omtn.2020.08.032.
15. Zhang Q., Li T., Wang Z., et al. lncRNA NR2F1-AS1 promotes breast cancer angiogenesis through activating IGF-1/IGF-1R/ERK pathway. J Cell Mol Med. 2020;24(14):8236-8247. doi:10.1111/jcmm.15499.
16. Zhang H., Liu B., Shi X., et al. Long noncoding RNAs: Potential therapeutic targets in cardiocerebrovascular diseases. Pharmacol Ther. 2021;222:107744. doi:10.1016/j.pharmthera.2020.107744.
17. Sun J., Chen G., Jing Y., et al. LncRNA Expression Profile of Human Thoracic Aortic Dissection by High-Throughput Sequencing. Cell Physiol Biochem. 2018;46(3):1027-1041. doi:10.1159/000488834.
18. Du L., Li X., Gao Q., et al. LncRNA nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) aggravates nucleus pulposus cell apoptosis and extracellular matrix degradation. Bioengineered. 2022;13(2):2746-2762. doi:10.1080/21655979.2021.2016087.
19. Ren P., Zhang H., Chang L., et al. LncRNA NR2F1-AS1 promotes proliferation and metastasis of ESCC cells via regulating EMT. Eur Rev Med Pharmacol Sci. 2020;24(7):3686-3693. doi:10.26355/eurrev_202004_20831.
20. Li R.F., Wu T.Y., Mou Y.Z., et al. Nr2f1b control venous specification and angiogenic patterning during zebrafish vascular development. J Biomed Sci. 201522:104. doi:10.1186/s12929-015-0209-0.
Review
For citations:
Shipulina S.A., Goncharova I.A., Zarubin A.A., Panfilov D.S., Kozlov B.N., Nazarenko M.S. DNA methylation patterns in the long noncoding RNA NR2F1-AS1 gene region in ascending aortic aneurysm and atherosclerosis. Medical Genetics. 2025;24(12):74-79. (In Russ.) https://doi.org/10.25557/2073-7998.2025.12.74-79
Views:
11
JATS XML
Email this article 