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J Vasc Res ; 52(6): 404-13, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27194055

RESUMO

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.


Assuntos
Aneurisma da Aorta Abdominal/genética , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Histonas/sangue , Linfócitos T/metabolismo , Acetilação , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/imunologia , Autoimunidade/genética , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/sangue , DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Histona Desacetilases/sangue , Histona Desacetilases/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro/sangue , RNA Mensageiro/genética , Linfócitos T/imunologia
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