DNA Methylation in Aortic Aneurysms of Different Localization

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Aortic aneurysm (AA) is a life-threatening condition, and aortic rupture that is the complication of AA in the absence of emergency surgery leads to death. Genetic (more often in thoracic AA – TAA) and environmental factors (in TAA and abdominal AA – AAA) contribute to the development of AA. This review summarizes the data of scientific publications devoted to the study of DNA methylation under the influence of AA risk factors, as well as in the cells of different parts of the aorta (thoracic, abdominal) in normal and pathological conditions. Changes in DNA methylation are observed in aortic and/or blood cells in the presence of AA risk factors (arterial hypertension, smoking, age, presence of comorbidities). Studies of DNA methylation in TAA and AAA are few and have been conducted using different approaches to sample formation, cell sample selection, and experimental methods. However, they provide convincing evidence of the altered DNA methylation status of genes selected for study using a candidate approach (in the AAA study), as well as of different genomic regions in genome-wide DNA methylation analysis (mainly in TAA studies). Genes localized in differentially methylated regions are associated with the functioning of the cardiovascular system and are involved in cellular and metabolic processes pathogenetically significant for the development of AA. In a number of cases, the association of DNA methylation levels with clinical parameters in AA has been established. These results indicate the prospect of expanding the studies of DNA methylation in AA, including the identification of new pathogenetically significant links in AA development.

Full Text

Restricted Access

About the authors

A. N. Kucher

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: maria.nazarenko@medgenetics.ru
Russian Federation, Tomsk, 634050

S. A. Shipulina

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: maria.nazarenko@medgenetics.ru
Russian Federation, Tomsk, 634050

I. A. Goncharova

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: maria.nazarenko@medgenetics.ru
Russian Federation, Tomsk, 634050

M. S. Nazarenko

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Author for correspondence.
Email: maria.nazarenko@medgenetics.ru
Russian Federation, Tomsk, 634050

References

  1. Mangum K.D., Farber M.A. Genetic and epigenetic regulation of abdominal aortic aneurysms // Clin. Genet. 2020. V. 97. № 6. P. 815–826. https://doi.org/10.1111/cge.13705
  2. Gouveia E Melo R., Silva Duarte G., Lopes A. et al. Incidence and prevalence of thoracic aortic aneurysms: A systematic review and meta-analysis of population-based studies // Semin. Thorac. Cardiovasc. Surg. 2022. V. 34. № 1. P. 1–16. https://doi.org/10.1016/j.jvs.2021.08.080
  3. Tomee S.M., Bulder R.M.A., Meijer C.A. et al. Excess mortality for abdominal aortic aneurysms and the potential of strict implementation of cardiovascular risk management: A multifaceted study integrating meta-analysis, National Registry, and PHAST and TEDY Trial Data // Eur. J. Vasc. Endovasc. Surg. 2023. V. 65. № 3. P. 348–357. https://doi.org/10.1016/j.ejvs.2022.11.019
  4. Isselbacher E.M., Preventza O., Hamilton Black J. 3rd et al. ACC/AHA Guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines // Circulation. 2022. V. 146. № 24. P. e334–e482. https://doi.org/10.1161/CIR.0000000000001106
  5. Ying A.J., Affan E.T. Abdominal aortic aneurysm screening: A systematic review and meta-analysis of efficacy and cost // Ann. Vasc. Surg. 2019. V. 4. P. 298–303.e3. https://doi.org/10.1016/j.avsg.2018.05.044
  6. Qian G., Adeyanju O., Olajuyin A., Guo X. Abdominal aortic aneurysm formation with a focus on vascular smooth muscle cells // Life (Basel). 2022. V. 12. № 2. P. 191. https://doi.org/10.3390/life12020191
  7. Zhou Z., Cecchi A.C., Prakash S.K., Milewicz D.M. Risk factors for thoracic aortic dissection // Genes (Basel). 2022. V. 13. № 10. https://doi.org/10.3390/genes13101814
  8. Gao J., Cao H., Hu G. et al. The mechanism and therapy of aortic aneurysms // Signal Transduct. Target. Ther. 2023. V. 8. № 1. P. 55. https://doi.org/10.1038/s41392-023-01325-7
  9. Duarte V.E., Yousefzai R., Singh M.N. Genetically triggered thoracic aortic disease: Who should be tested? // Methodist Debakey Cardiovasc. J. 2023. V. 19. № 2. P. 24–28. https://doi.org/10.14797/mdcvj.1218
  10. van de Luijtgaarden K.M., Heijsman D., Maugeri A. et al. First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm // Hum. Genet. 2015. V. 134. № 8. P. 881–893. https://doi.org/10.1007/s00439-015-1567-0
  11. Gyftopoulos A., Ziganshin B.A., Elefteriades J.A., Ochoa Chaar C.I. Comparison of genes associated with thoracic and abdominal aortic aneurysms // Aorta (Stamford). 2023. V. 11. № 3. P. 125–134. https://doi.org/10.1055/s-0043-57266
  12. Lino Cardenas C.L., Kessinger C.W., Cheng Y. et al. An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm // Nat. Commun. 2018. V. 9. № 1. P. 1009. https://doi.org/10.1038/s41467-018-03394-7
  13. Lino Cardenas C.L., Kessinger C.W., MacDonald C. et al. Inhibition of the methyltranferase EZH2 improves aortic performance in experimental thoracic aortic aneurysm // JCI Insight. 2018. V. 3. № 5. https://doi.org/10.1172/jci.insight.97493
  14. Portelli S.S., Robertson E.N., Malecki C. et al. Epigenetic influences on genetically triggered thoracic aortic aneurysm // Biophys. Rev. 2018. V. 10. № 5. P. 1241–1256. https://doi.org/10.1007/s12551-018-0460-1
  15. Chang Z., Zhao G., Zhao Y. et al. BAF60a deficiency in vascular smooth muscle cells prevents abdominal aortic aneurysm by reducing inflammation and extracellular matrix degradation // Arterioscler. Thromb. Vasc. Biol. 2020. V. 40. № 10. P. 2494–2507. https://doi.org/10.1161/ATVBAHA.120.314955
  16. Tasopoulou K.M., Argiriou C., Tsaroucha A.K., Georgiadis G.S. Circulating miRNAs as biomarkers for diagnosis, surveillance, and postoperative follow-up of abdominal aortic aneurysms // Ann. Vasc. Surg. 2023. V. 93. P. 387–404. https://doi.org/10.1016/j.avsg.2023.02.029
  17. Zhang X., Liu S., Weng X. et al. Brg1 trans-activates endothelium-derived colony stimulating factor to promote calcium chloride induced abdominal aortic aneurysm in mice // J. Mol. Cell. Cardiol. 2018. V. 125. P. 6–17. https://doi.org/10.1016/j.yjmcc.2018.10.012
  18. Krishna S.M., Dear A.E., Norman P.E., Golledge J. Genetic and epigenetic mechanisms and their possible role in abdominal aortic aneurysm // Atherosclerosis. 2010. V. 212. № 1. P. 16–29. https://doi.org/10.1016/j.atherosclerosis.2010.02.008.
  19. Han Y., Tanios F., Reeps C. et al. Histone acetylation and histone acetyltransferases show significant alterations in human abdominal aortic aneurysm // Clin. Epigenetics. 2016. V. 8. P. 3. https://doi.org/10.1186/s13148-016-0169-6
  20. Jiang H., Xia Q., Xin S. et al. Abnormal epigenetic modifications in peripheral T cells from patients with abdominal aortic aneurysm are correlated with disease development // J. Vasc. Res. 2015. V. 52. № 6. P. 404–413. https://doi.org/10.1159/000445771
  21. Toghill B.J., Saratzis A., Freeman P.J. et al. SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells // Clin. Epigenetics. 2018. V. 1. P. 29. https://doi.10.1186/s13148-018-0460-9
  22. D’Amico F., Doldo E., Pisano C. et al. Specific miRNA and gene deregulation characterize the increased angiogenic remodeling of thoracic aneurysmatic aortopathy in Marfan syndrome // Int. J. Mol. Sci. 2020. V. 21. № 18. https://doi.org/10.3390/ijms21186886
  23. Greenway J., Gilreath N., Patel S. et al. Profiling of histone modifications reveals epigenomic dynamics during abdominal aortic aneurysm formation in mouse models // Front. Cardiovasc. Med. 2020. V. 7. https://doi.org/10.3389/fcvm.2020.595011
  24. Mangum K., Gallagher K., Davis F.M. The role of epigenetic modifications in abdominal aortic aneurysm pathogenesis // Biomolecules. 2022. V. 12. № 2. https://doi.org/10.3390/biom12020172
  25. Rombouts K.B., van Merrienboer T.A.R., Ket J.C.F. et al. The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections // Eur. J. Clin. Invest. 2022. V. 52. № 4. https://doi.org/10.1111/eci.13697
  26. Eilenberg W., Zagrapan B., Bleichert S. et al. Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms // Transl. Res. 2021. V. 233. P. 32–46. https://doi.org/10.1016/j.trsl.2021.02.003
  27. Bararu Bojan Bararu I., Pleșoianu C.E., Badulescu O.V. et al. Molecular and cellular mechanisms involved in aortic wall aneurysm development // Diagnostics (Basel, Switzerland). 2023. V. 13. V. 2. https://doi.org/10.3390/diagnostics13020253
  28. Quintana R.A., Taylor W.R. Cellular mechanisms of aortic aneurysm formation // Circ. Res. 2019. V. 124. № 4. P. 607–618. https://doi.org/10.1161/CIRCRESAHA.118.313187
  29. Mishra S., Raval M., Kachhawaha A.S. et al. Aging: Epigenetic modifications // Prog. Mol. Biol. Transl. Sci. 2013. V. 197. P. 171–209. https://doi.org/10.1016/bs.pmbts.2023.02.002
  30. Wang X., Falkner B., Zhu H. et al. A genome-wide methylation study on essential hypertension in young African American males // PLoS OnE. 2013. V. 8. P. 451. https://doi.org/10.1371/journal.pone.0053938
  31. Wise I.A., Charchar F.J. Epigenetic modifications in essential hypertension // Int. J. Mol. Sci. 2016. V. 17. № 4. https://doi.org/10.3390/ijms17040451
  32. Кучер А.Н., Назаренко М.С., Марков А.В. и др. Вариабельность профилей метилирования CpG-сайтов генов микроРНК в лейкоцитах и тканях сосудов при атеросклерозе у человека // Биохимия. 2017. Т. 82. № 6. С. 923–933.)
  33. Liu P., Zhang J., Du D. et al. Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis // Clin. Epigenetics. 2021. V. 13. № 1. P. 124. https://doi.org/10.1186/s13148-021-01110-9
  34. Dai Y., Chen D., Xu T. DNA methylation aberrant in atherosclerosis // Front. Pharmacol. 2022. V. 13.. https://doi.org/10.3389/fphar.2022.815977
  35. Liu S., Li Y., Wei X. et al. Genetic analysis of DNA methylation in dyslipidemia: a case-control study // PeerJ. 2022. V. 10. https://doi.org/10.7717/peerj.14590
  36. Chu D.T., Bui N.L., Vu Thi H. et al. Role of DNA methylation in diabetes and obesity // Prog. Mol. Biol. Transl. Sci. 2023. V. 197. P. 153–170. https://doi.org/10.1016/bs.pmbts.2023.01.008
  37. da Silva Rodrigues G., Noronha N.Y., Almeida M.L. et al. Exercise training modifies the whole blood DNA methylation profile in middle-aged and older women // J. Appl. Physiol. (1985). 2023. V. 134. № 3. P. 610–621. https://doi.org/10.1152/japplphysiol.00237.2022
  38. Krolevets M., Cate V.T., Prochaska J.H. et al. DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites // Clin. Epigenetics. 2023. V. 15. № 1 P. 56. https://doi.org/10.1186/s13148-023-01468-y
  39. Smolarek I., Wyszko E., Barciszewska A.M. et al. Global DNA methylation changes in blood of patients with essential hypertension // Med. Sci. Monit. 2010. V. 16. № 3. P. CR149–CR155.
  40. Kato N., Loh M., Takeuchi F. et al. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation // Nat. Genet. 2015. V. 47. № 11. P. 1282–1293. https://doi.org/10.1038/ng.3405
  41. Zhang Y., Mei J., Li J. et al. DNA Methylation in Atherosclerosis: A new perspective // Evid. Based Complement. Alternat. Med. 2021. V. 2021. https://doi.org/10.1155/2021/6623657
  42. Chen Y., Liang L., Wu C. et al. Epigenetic control of vascular smooth muscle cell function in atherosclerosis: A role for DNA methylation // DNA Cell Biol. 2022. V. 41. № 9. P. 824–837. https://doi.org/10.1089/dna.2022.0278
  43. Пальцева Е.М. Аневризмы аорты: этиология и патоморфология // Мол. медицина. 2015. Т. 4. С., 3–10.)
  44. Кучер А.Н., Назаренко М.С. Роль микро-РНК при атерогенезе // Кардиология. 2017. V. 57. № 9. P. 65–76. https://doi.org/10.18087/cardio.2017.9.10022)
  45. Bell C.G., Xia Y., Yuan W. et al. Novel regional age-associated DNA methylation changes within human common disease-associated loci // Genome Biol. 2016. V. 17. № 1. P. 193. https://doi.org/10.1186/s13059-016-1051-8
  46. Balint B., Bernstorff I.G.L., Schwab T., Schäfers H.J. Age-dependent phenotypic modulation of smooth muscle cells in the normal ascending aorta // Front. Cardiovasc Med. 2023. V. 10. https://doi.org/10.3389/fcvm.2023.1114355.
  47. Wang Z., Zhao J., Sun J. et al. Sex-dichotomous effects of NOS1AP promoter DNA methylation on intracranial aneurysm and brain arteriovenous malformation // Neurosci. Lett. 2016. V. 621. P. 47–53. https://doi.org/10.1016/j.neulet.2016.04.016
  48. Fragou D., Pakkidi E., Aschner M. et al. Smoking and DNA methylation: Correlation of methylation with smoking behavior and association with diseases and fetus development following prenatal exposure // Food Chem. Toxicol. 2019. V. 129. P. 312–327. https://doi.org/10.1016/j.fct.2019.04.059
  49. Forte A., Galderisi U., Cipollaro M. et al. Epigenetic regulation of TGF-β1 signalling in dilative aortopathy of the thoracic ascending aorta // Clin. Sci. (Lond). 2016. V. 130. № 16. P. 1389–1405. https://doi.org/10.1042/CS20160222
  50. Davis F.M., Gallagher K.A. Epigenetic mechanisms in monocytes/macrophages regulate inflammation in cardiometabolic and vascular disease // Arterioscler. Thromb. Vasc. Biol. 2019. V. 39. № 4. P. 623–634. https://doi.org/10.1161/ATVBAHA.118.312135
  51. Davis F.M., Tsoi L.C., Melvin W.J. et al. Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms // J. Exp. Med. 2021. V. 218. № 6. https://doi. org/10.1084/jem.20201839
  52. Zhao G., Zhao Y., Lu H. et al. BAF60c prevents abdominal aortic aneurysm formation through epigenetic control of vascular smooth muscle cell homeostasis // J. Clin. Invest. 2022. V. 132. № 21. https://doi.org/10.1172/JCI158309
  53. 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. V. 18. № 4. P. E134–E139. https://doi.org/10.1532/hsf.1247
  54. Matsumura H., Nakano Y., Ochi H. et al. H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters // J. Biomed. Sci. 2017. V. 24. № 1. P. 91. https://doi.org/10.1186/s12929-017-0397-x
  55. 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. V. 113. № 6. P. 692–704. https://doi.org/10.1093/cvr/cvx050
  56. Björck H.M., Du L., Pulignani S. et al. Altered DNA methylation indicates an oscillatory flow mediated epithelial-to-mesenchymal transition signature in ascending aorta of patients with bicuspid aortic valve // Sci. Rep. 2018. V. 8. № 1. P. 2777. https://doi.org/10.1038/s41598-018-20642-4
  57. Lian R., Zhang G., Yan S. et al. Identification of molecular regulatory features and markers for acute type A aortic dissection // Comput. Math. Methods. Med. 2021. V. 2021. https://doi.org/10.1155/2021/6697848
  58. Chen Y., Xu X., Chen Z. et al. DNA methylation alternation in Stanford A acute aortic dissection /BMC Cardiovasc. Disord. 2022. V. 22. № 1. P. 455. https://doi.org/10.1186/s12872-022-02882-5
  59. Ryer E.J., Ronning K.E., Erdman R. et al. The potential role of DNA methylation in abdominal aortic aneurysms // Int. J. Mol. Sci. 2015. V. 16. № 5. P. 11259–11275. https://doi.org/10.3390/ijms160511259
  60. Krishna S.M., Seto S.W., Jose R.J. et al. Wnt signaling pathway inhibitor sclerostin inhibits angiotensin II-induced aortic aneurysm and atherosclerosis // Arterioscler. Thromb. Vasc. Biol. 2017. V. 37. № 3. P. 553–566. https://doi.org/10.1161/ATVBAHA.116.308723
  61. Xia Q., Zhang J., Han Y. et al. Epigenetic regulation of regulatory T cells in patients with abdominal aortic aneurysm // FEBS Open Bio. 2019. V. 9. № 6. P. 1137–1143. https://doi.org/10.1002/2211-5463.12643
  62. Zhong L., He X., Si X. et al. SM22α (Smooth Muscle 22α) prevents aortic aneurysm formation by inhibiting smooth muscle cell phenotypic switching through suppressing reactive oxygen species/NF-κB (Nuclear Factor-κB) // Arterioscler. Thromb. Vasc. Biol. 2019. V. 39. № 1. P. e10–e25. https://doi.org/10.1161/ATVBAHA.118.311917
  63. Skorvanova M., Matakova T., Skerenova M. et al. Methylation of MMP2, TIMP2, MMP9 and TIMP1 in abdominal aortic aneurysm // Bratisl. Lek. Listy. 2020. V. 121. № 10. P. 717–721. https://doi.org/10.4149/BLL_2020_117
  64. Vats S., Sundquist K., Wang X. et al. Associations of global DNA methylation and homocysteine levels with abdominal aortic aneurysm: A cohort study from a population-based screening program in Sweden // Int. J. Cardiol. 2020. V. 321. P. 137–142. https://doi.org/10.1016/j.ijcard.2020.06.022
  65. Simões G., Pereira T., Caseiro A. Matrix metaloproteinases in vascular pathology // Microvasc. Res. 2022. V. 143. https://doi.org/10.1016/j.mvr.2022.104398
  66. Stepien K.L., Bajdak-Rusinek K., Fus-Kujawa A. et al. Role of extracellular matrix and inflammation in abdominal aortic aneurysm // Int. J. Mol. Sci. 2022. V. 23. № 19. https://doi.org/10.3390/ijms231911078
  67. 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. V. 64. № 3. https://doi.org/10.1016/j.jlr.2023.100338
  68. Maleki S., Kjellqvist S., Paloschi V. et al. Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves // Sci. Rep. 2016. V. 6. https://doi.org/10.1038/srep35712
  69. Narayanan N., Tyagi N., Shah A. et al. Hyperhomocysteinemia during aortic aneurysm: a plausible role of epigenetics // Int. J. Physiol. Pathophysiol. Pharmacol. 2013. V. 5. № 1. P. 32–42.
  70. Takada S., Berezikov E., Choi Y.L. et al. Potential role of miR-29b in modulation of Dnmt3a and Dnmt3b expression in primordial germ cells of female mouse embryos // RNA. 2009. V. 15. P. 1507–1514. https://doi.org/10.1261/rna.1418309
  71. Chen K.C., Wang Y.S., Hu C.Y. et al. OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: A novel mechanism for cardiovascular diseases // FASEB J. 2011. V. 25. № 5. P. 1718–1728. https://doi.org/10.1096/fj.10-174904
  72. Rabkin S.W. The role matrix metalloproteinases in the production of aortic aneurysm // Prog. Mol. Biol. Transl Sci. 2017. V. 147. P. 239–265. https://doi.org/10.1016/bs.pmbts.2017.02.002
  73. Li T., Jiang B., Li X. et al. Serum matrix metalloproteinase-9 is a valuable biomarker for identification of abdominal and thoracic aortic aneurysm: a case-control study // BMC Cardiovasc. Disord. 2018. V. 18. № 1. P. 202. https://doi.org/10.1186/s12872-018-0931-0
  74. Shafeeque C.M., Sathyan S., Saradalekshmi K.R. et al. Methylation map genes can be critical in determining the methylome of intracranial aneurysm patients // Epigenomics. 2020. V. 12. № 10. P. 859–871. https://doi.org/10.2217/epi-2019-0280
  75. Galán M., Varona S., Orriols M. et al. Induction of histone deacetylases (HDACs) in human abdominal aortic aneurysm: therapeutic potential of HDAC inhibitors // Dis. Model. Mech. 2016. V. 9. № 5. P. 541–552. https://doi.org/10.1242/dmm.024513
  76. Iyer V., Rowbotham S., Biros E. et al. A systematic review investigating the association of microRNAs with human abdominal aortic aneurysms // Atherosclerosis. 2017. V. 261. P. 78–89. https://doi.10.1016/j.atherosclerosis.2017.03.010
  77. Li Y., Maegdefessel L. Non-coding RNA contribution to thoracic and abdominal aortic aneurysm disease development and progression // Front. Physiol. 2017. V. 8. https://doi.org/10.3389/fphys.2017.00429
  78. Zalewski D.P., Ruszel K.P., Stępniewski A. et al. Dysregulation of microRNA modulatory network in abdominal aortic aneurysm // J. Clin. Med. 2020. V. 9. № 6. P. 1974. https://doi.org/10.3390/jcm9061974
  79. Xu Y., Yang S., Xue G. The role of long non-coding RNA in abdominal aortic aneurysm // Front. Genet. 2023. V. 14. https://doi.org/10.3389/fgene.2023.115389

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Russian Academy of Sciences