title: [The effect of miR-124 on homocysteine-induced atherosclerosis via promoter region DNA methylation in ApoE(-/-) mice].
abstract: The aim of the present study is to explore the role of miR-124 and its promoter region DNA methylation in homocysteine (Hcy)-induced atherosclerosis. ApoE(-/-) mice were fed with hypermethionine diet for 16 weeks to duplicate hyperhomocysteinemia model. Meanwhile, a normal control group (C57BL/6J mice fed with normal diet, N-control) and a model control group (ApoE(-/-) mice fed with normal diet, A-control) were set. The degree of atherosclerosis was observed by HE and oil red O staining. Automatic biochemical analyzer was used to detect the serum levels of Hcy. Foam cell model was duplicated and oil red O staining was used to confirm whether the model was successfully established. And foam cells were stimulated with 0, 50, 100, 200, 500 μmol/L Hcy and 50 μmol/L Hcy + 10 μmol/L AZC respectively. Real-time quantitative PCR (RT-qPCR) was used to detect the expressions of miR-124 in mice aorta and foam cells; Nested landing methylation specific PCR (nMS-PCR) was used to detect the levels of miR-124 promoter DNA methylation in mice aorta and foam cells. Meanwhile, the effects of DNA methylation inhibitor AZC on miR-124 expression were observed at the cellular level. The effect of miR-124 promoter DNA methylation status on lipid accumulation in foam cells was observed by oil red O staining. The results showed that compared with model control group, the serum levels of Hcy in high methionine group were significantly increased (P < 0.01) and developed aortic atherosclerotic plaque, the expression of miR-124 was markedly decreased (P < 0.01), while the levels of miR-124 promoter DNA methylation were significantly increased (P < 0.01). Given different levels of Hcy, the expression of miR-124 in foam cells was decreased, while the levels of miR-124 promoter DNA methylation were increased in a dose-dependent manner (P < 0.05, P < 0.01). AZC reversed the results of mentioned indices as above markedly (P < 0.05). Downregulation of miR-124 may play a role in Hcy-induced atherosclerosis and its promoter DNA methylation status may be an important mechanism in this process.
authors.affiliation: College of Laboratory Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Infectious Disease of General Hospital, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: College of Preclinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: An-Ning
authors.initials: AN
authors.lastname: Yang
authors.affiliation: College of Laboratory Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Cheng-Jian
authors.initials: CJ
authors.lastname: Cao
authors.affiliation: College of Preclinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Fan-Qi
authors.initials: FQ
authors.lastname: Kong
authors.affiliation: College of Preclinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Xian-Mei
authors.initials: XM
authors.lastname: Liu
authors.affiliation: College of Preclinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Yang
authors.affiliation: College of Preclinical Medicine, Ningxia Medical University, Yinchuan 750004, China. jwcjyd@163.com.
authors.forename: Yi-Deng
authors.initials: YD
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E; D050197:Atherosclerosis / Q000139:chemically induced / Q000235:genetics*; D019175:DNA Methylation; D004032:Diet; D005487:Foam Cells / Q000378:metabolism; D006710:Homocysteine / Q000009:adverse effects; D020138:Hyperhomocysteinemia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D001057:Apolipoproteins E; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D006710:Homocysteine