Aberrant promoter methylation of multiple genes in VSMC proliferation induced by Hcy.
Mol Med Rep
; 16(5): 7775-7783, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28944836
ABSTRACT
Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in atherosclerosis (AS), and homocysteine (Hcy) is an independent risk factor for AS. However, the underlying mechanisms are still lagging. Studies have used the combination of methylation of promoters of multiple genes to diagnose tumors, thus the aim of the current study was to investigate the role of methylation status of several genes in VSMCs treated with Hcy. CpG islands were identified in the promoters of plateletderived growth factor (PDGF), p53, phosphatase and tensin homologue on chromosome 10 (PTEN) and mitofusin 2 (MFN2). Hypomethylation was observed to occur in the promoter region of PDGF, hypermethylation in p53, PTEN and MFN2, and hypomethylation in two global methylation indicators, aluminium (Alu) and long interspersed nucleotide element1 (Line1). This was accompanied by an increase in the expression of PDGF, and reductions of p53, PTEN and MFN2, both in mRNA and protein levels. An elevation of Sadenosylmethionine (SAM) and a reduction of Sadenosylhomocysteine (SAH) and the SAM/SAH ratio were also identified. In conclusion, Hcy impacted methylation the of ASassociated genes and global methylation status that mediate the cell proliferation, which may be a character of VSMCs treated with Hcy. The data provided evidence for mechanisms of VSMCs proliferation in AS induced by Hcy and may provide a new perspective for AS induced by Hcy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regiões Promotoras Genéticas
/
Metilação de DNA
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Miócitos de Músculo Liso
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Epigênese Genética
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Homocisteína
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article