Molecular Biology

, Volume 47, Issue 3, pp 352–357 | Cite as

DNA methylation profiling of the vascular tissues in the setting of atherosclerosis

  • M. S. Nazarenko
  • A. V. Markov
  • I. N. Lebedev
  • A. A. Sleptsov
  • A. V. Frolov
  • O. L. Barbarash
  • L. S. Barbarash
  • V. P. Puzyrev
Genomics. Transcriptomics

Abstract

Currently, the question of epigenetic mechanisms of gene regulation in the context of cardiovascular diseases is of considerable interest. Here, DNA methylation profiles of vascular tissues of atherosclerotic patients have been analyzed for the first time using the Infinium Human Methylation27 BeadChip microarray (Illumina, United States). As the result, within 286 genes, 314 CpG sites that varied significantly in the level of DNA methylation between the tissue samples of carotid (in the area of atherosclerotic plaques and nearby macroscopically intact tissues of the vascular wall) and mammary arteries, as well as saphenous veins have been identified. The most pronounced differences in the methylation level was registered for CpG sites of homeobox genes HOXA2 and HOXD4, as well as the imprinted MEST gene. In particular, these genes were found to be hypomethylated in the carotid atherosclerotic plaques compared to their methylation patterns in intact tissues of internal mammary arteries and saphenous veins.

Keywords

DNA methylation atherosclerosis Infinium Human Methylation27 BeadChip 

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References

  1. 1.
    Ballestar E., Esteller M. 2008. Epigenetic gene regulation in cancer. Adv. Genet. 61, 247–267.PubMedCrossRefGoogle Scholar
  2. 2.
    Feinberg A.P., Irizarry R.A., Fradin D. et al. 2010. Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci. Transl. Med. 2, 49–67.CrossRefGoogle Scholar
  3. 3.
    Turunen M.P., Aavik E., Yla-Herttuala S. 2009. Epigenetics and atherosclerosis. Biochim. Biophys. Acta. 1790, 886–891.PubMedCrossRefGoogle Scholar
  4. 4.
    Hiltunen M.O., Turunen M.P., Hakkinen T.P. et al. 2002. DNA hypomethylation and methyltransferase expression in atherosclerotic lesions. Vasc. Med. 7, 5–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Post W.S., Goldschmidt-Clermont P.J., Wilhide C.C., et al. 1999. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovasc. Res. 43, 985–991.PubMedCrossRefGoogle Scholar
  6. 6.
    Kim J., Kim J.Y., Song K.S., et al. 2007. Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. Biochim. Biophys. Acta. 1772, 72–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhu S., Goldschmidt-Clermont P.J., Dong C. 2005. Inactivation of monocarboxylate transporter MCT3 by DNA methylation in atherosclerosis. Circulation. 112, 1353–1361.PubMedCrossRefGoogle Scholar
  8. 8.
    Zawadzki C., Chatelain N., Delestre M., et al. 2009. Tissue factor pathway inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques. Atherosclerosis. 204, e4–e14.PubMedCrossRefGoogle Scholar
  9. 9.
    Castillo-Diaz S.A., Garay-Sevilla M.E., Hernandez-Gonzalez M.A., et al. 2010. Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries. Int. J. Mol. Med. 26, 691–700.PubMedGoogle Scholar
  10. 10.
    Nazarenko M.S., Puzyrev V.P., Lebedev I.N. et al. 2011. Methylation profiling of human atherosclerotic plaques. Mol. Biol. (Moscow). 45, 561–566.CrossRefGoogle Scholar
  11. 11.
    Bibikova M., Le J., Barnes B., et al. 2009. Genomewide DNA methylation profiling using Infinium assay. Epigenomics. 1, 177–200.PubMedCrossRefGoogle Scholar
  12. 12.
  13. 13.
  14. 14.
  15. 15.
    Baccarelli A., Rienstra M., Benjamin E.J. 2010. Cardiovascular epigenetics: Basic concepts and results from animal and human studies. Circ. Cardiovasc. Genet. 3, 567–573.PubMedCrossRefGoogle Scholar
  16. 16.
    Jones P.A. 2012. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nature Rev. Genet. 13, 484–492.PubMedCrossRefGoogle Scholar
  17. 17.
    Irizarry R.A., Ladd-Acosta C., Wen B., et al. 2009. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nature Genet. 41, 178–186.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  • M. S. Nazarenko
    • 1
    • 2
  • A. V. Markov
    • 1
  • I. N. Lebedev
    • 1
    • 2
  • A. A. Sleptsov
    • 1
  • A. V. Frolov
    • 3
  • O. L. Barbarash
    • 3
  • L. S. Barbarash
    • 3
  • V. P. Puzyrev
    • 1
    • 2
  1. 1.Research Institute of Medical Genetics, Siberian BranchRussian Academy of Medical SciencesTomskRussia
  2. 2.Ministry of Healthcare of the Russian FederationSiberian State Medical UniversityTomskRussia
  3. 3.Research Institute for Complex Issues of Cardiovascular Diseases, Siberian BranchRussian Academy of Medical SciencesKemerovoRussia

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