title: Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation.
abstract: 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.
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.|Institution of Medical Science of Ningxia, Yinchuan, Ningxia, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiaoling
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Li
authors.initials: L
authors.lastname: ShuQiang
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Ma
authors.initials: M
authors.lastname: Shengchao
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Anning
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ning
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Li
authors.initials: L
authors.lastname: Nan
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yuexia
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiaoming
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guizhong
authors.affiliation: Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yideng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D035683:MicroRNAs; C541873:Mirn92 microRNA, mouse; D006710:Homocysteine; D000071221:Enhancer of Zeste Homolog 2 Protein