A Comparison of Genome-Wide DNA Methylation Patterns between Different Vascular Tissues from Patients with Coronary Heart Disease

被引:46
作者
Nazarenko, Maria S. [1 ,3 ]
Markov, Anton V. [1 ,3 ]
Lebedev, Igor N. [2 ,3 ]
Freidin, Maxim B. [1 ]
Sleptcov, Aleksei A. [1 ,3 ]
Koroleva, Iuliya A. [1 ]
Frolov, Aleksei V. [4 ]
Popov, Vadim A. [5 ]
Barbarash, Olga L. [5 ]
Puzyrev, Valery P. [1 ,3 ]
机构
[1] Res Inst Med Genet, Lab Populat Genet, Tomsk, Russia
[2] Res Inst Med Genet, Lab Cytogenet, Tomsk, Russia
[3] Tomsk State Univ, Lab Human Ontogenet, Tomsk 634050, Russia
[4] Res Inst Complex Problems Cardiovasc Dis, Lab Neurovascular Pathol, Kemerovo, Russia
[5] Res Inst Complex Problems Cardiovasc Dis, Dept Multifocal Atherosclerosis, Kemerovo, Russia
来源
PLOS ONE | 2015年 / 10卷 / 04期
基金
俄罗斯科学基金会;
关键词
GENE-EXPRESSION; ATHEROSCLEROSIS; ARTERIES; ISLANDS;
D O I
10.1371/journal.pone.0122601
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:15
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