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[This corrects the article DOI: 10.1371/journal.pone.0167744.].
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Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases, such as atherosclerosis. HHcy promotes atherogenesis by modifying the histone methylation patterns and miRNA regulation. In this study, we investigated the effects of homocysteine (Hcy) on the expression of enhancer of zeste homolog 2 (EZH2), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased EZH2 expression, which is regulated by miR-92a. The levels of EZH2 and H3K27me3 were increased in the aorta of ApoE-/- mice fed a high-methionine diet for 16 weeks, whereas miR-92a expression was decreased. Over-expression of EZH2 increased H3K27me3 level and the accumulation of total cholesterol and triglycerides in the foam cells. Furthermore, upregulation of miR-92a reduced EZH2 expression in the foam cells. These data suggested that EZH2 plays a key role in Hcy-mediated lipid metabolism disorders, and that miR-92a may be a novel therapeutic target in Hcy-related atherosclerosis.
Assuntos
Apolipoproteínas E/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Hiper-Homocisteinemia/genética , MicroRNAs/genética , Regulação para Cima , Animais , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/metabolismo , Linhagem Celular , Regulação para Baixo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Deleção de Genes , Homocisteína/metabolismo , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismoRESUMO
Aim To explore the effect of miRNA-143 ( miR-1 4 3 ) on homocysteine ( Hcy ) induced-vascular smooth muscle cells ( VSMCs ) proliferation and the mechanism .Methods VSMCs were cultured and in-cubated with Hcy by using primary cultured method . Then, cells were treated with different concentrations of Hcy and folate .VSMCs proliferation was determined with MTT assay , miR-143 was measured by qRT-PCR, and methylation of miR-143 was determined with meth-ylated PCR.Results After cells were treated with dif-ferent concentrations of Hcy , the proliferation of VSMCs was significantly increased , mRNA expression of miR-143 was decreased and methylation of miR-143 was increased .The proliferation of VSMCs was signifi-cantly decreased when transfected VSMCs with miR-143 precursor , and cell proliferation was increased by using miR-143 inhibitor transfection .Conclusion Hy-pomethylation of miR-143 may inhibit VSMCs prolifera-tion.
