A comparison of genome-wide DNA methylation patterns between different vascular tissues from patients with coronary heart disease

PLoS One. 2015 Apr 9;10(4):e0122601. doi: 10.1371/journal.pone.0122601. eCollection 2015.

Abstract

Epigenetic mechanisms of gene regulation in context of cardiovascular diseases are of considerable interest. So far, our current knowledge of the DNA methylation profiles for atherosclerosis affected and healthy human vascular tissues is still limited. Using the Illumina Infinium Human Methylation27 BeadChip, we performed a genome-wide analysis of DNA methylation in right coronary artery in the area of advanced atherosclerotic plaques, atherosclerotic-resistant internal mammary arteries, and great saphenous veins obtained from same patients with coronary heart disease. The resulting DNA methylation patterns were markedly different between all the vascular tissues. The genes hypomethylated in athero-prone arteries to compare with atherosclerotic-resistant arteries were predominately involved in regulation of inflammation and immune processes, as well as development. The great saphenous veins exhibited an increase of the DNA methylation age in comparison to the internal mammary arteries. Gene ontology analysis for genes harboring hypermethylated CpG-sites in veins revealed the enrichment for biological processes associated with the development. Four CpG-sites located within the MIR10B gene sequence and about 1 kb upstream of the HOXD4 gene were also confirmed as hypomethylated in the independent dataset of the right coronary arteries in the area of advanced atherosclerotic plaques in comparison with the other vascular tissues. The DNA methylation differences observed in vascular tissues of patients with coronary heart disease can provide new insights into the mechanisms underlying the development of pathology and explanation for the difference in graft patency after coronary artery bypass grafting surgery.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Coronary Disease / genetics*
  • Coronary Disease / metabolism
  • Coronary Disease / pathology
  • Coronary Vessels / metabolism*
  • Coronary Vessels / pathology
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mammary Arteries / metabolism*
  • Mammary Arteries / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Molecular Sequence Annotation
  • Organ Specificity
  • Plaque, Atherosclerotic / genetics*
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Saphenous Vein / metabolism*
  • Saphenous Vein / pathology

Substances

  • Homeodomain Proteins
  • MIRN10 microRNA, human
  • MicroRNAs

Grants and funding

This research was supported by the President’s Grant for the Leading Scientific Schools of Russian Federation (№ 14.120.14.5096-SSch), by the Russian Scientific Fund (№ 14-15-00305) and by the National Program of Russian Academy of Medical Sciences «Human Proteome». The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.