Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

J Vasc Res. 2015;52(6):404-13. doi: 10.1159/000445771. Epub 2016 May 19.

Abstract

Background: Increasing evidence suggests that abdominal aortic aneurysm (AAA) is a T-cell-mediated autoimmune condition. This study investigates the epigenetic modifications that occur in the T cells of AAA patients and evaluates the correlation of these modifications with disease development.

Methods and results: Peripheral T cells were collected from 101 AAA patients and 102 healthy controls (HCs). DNA methylation and histone acetylation levels were measured by ELISA. Methyl-CpG-binding domain, DNA methyltransferase (DNMT) and histone deacetylase (HDAC) mRNA levels were determined by real-time PCR. DNA from the T cells of the AAA patients exhibited significant hypomethylation compared with the HCs (1.6-fold, p < 0.0001). Expression of DNMT1 at the mRNA level in the T cells of the AAA patients was 1.52-fold lower than that of the HCs (p < 0.0001). The extent of DNA methylation in the AAA patients was negatively correlated with the corresponding aortic diameter (r = -0.498, p < 0.0001). H3 (1.59-fold, p < 0.0001) and H3K14 (2.15-fold, p < 0.0001) acetylation levels in the T cells of the AAA patients were higher than those of the HCs, but the HDAC1 mRNA level was 2.33-fold lower than that of the HCs (p < 0.0001).

Conclusions: DNA methylation and the histone modification status are significantly altered in the T cells of AAA patients. These changes could play a pivotal role in the activation of pathological immune responses and may influence AAA development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adult
  • Aged
  • Aged, 80 and over
  • Aortic Aneurysm, Abdominal / blood
  • Aortic Aneurysm, Abdominal / diagnosis
  • Aortic Aneurysm, Abdominal / genetics*
  • Aortic Aneurysm, Abdominal / immunology
  • Autoimmunity / genetics
  • Case-Control Studies
  • CpG Islands*
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / blood
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation*
  • DNA-Binding Proteins / blood
  • DNA-Binding Proteins / genetics
  • Epigenesis, Genetic*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Histone Deacetylases / blood
  • Histone Deacetylases / genetics
  • Histones / blood*
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • RNA, Messenger / blood
  • RNA, Messenger / genetics
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • DNA-Binding Proteins
  • Histones
  • MBD2 protein, human
  • RNA, Messenger
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • Histone Deacetylases