PMID- 27936205 OWN - NLM STAT- MEDLINE DCOM- 20170710 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 12 DP - 2016 TI - Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation. PG - e0167744 LID - 10.1371/journal.pone.0167744 [doi] LID - e0167744 AB - 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. FAU - Xiaoling, Yang AU - Xiaoling Y AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Institution of Medical Science of Ningxia, Yinchuan, Ningxia, China. FAU - Li, Zhao AU - Li Z AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - ShuQiang, Li AU - ShuQiang L AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Shengchao, Ma AU - Shengchao M AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Anning, Yang AU - Anning Y AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Ning, Ding AU - Ning D AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Nan, Li AU - Nan L AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Yuexia, Jia AU - Yuexia J AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Xiaoming, Yang AU - Xiaoming Y AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Guizhong, Li AU - Guizhong L AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Yideng, Jiang AU - Yideng J AD - Basic Medical School, Ningxia Medical University, Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. LA - eng PT - Journal Article DEP - 20161209 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Apolipoproteins E) RN - 0 (MicroRNAs) RN - 0 (Mirn92 microRNA, mouse) RN - 0LVT1QZ0BA (Homocysteine) RN - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) SB - IM EIN - PLoS One. 2020 Oct 12;15(10):e0240762. PMID: 33045026 MH - Animals MH - Apolipoproteins E/*genetics MH - Atherosclerosis/etiology/genetics/metabolism MH - Cell Line MH - Down-Regulation MH - Enhancer of Zeste Homolog 2 Protein/*genetics/metabolism MH - Gene Deletion MH - Homocysteine/metabolism MH - Humans MH - Hyperhomocysteinemia/complications/*genetics/metabolism MH - Lipid Metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics/metabolism MH - *Up-Regulation PMC - PMC5147974 COIS- The authors have declared that no competing interests exist. EDAT- 2016/12/10 06:00 MHDA- 2017/07/14 06:00 PMCR- 2016/12/09 CRDT- 2016/12/10 06:00 PHST- 2016/07/05 00:00 [received] PHST- 2016/11/19 00:00 [accepted] PHST- 2016/12/10 06:00 [entrez] PHST- 2016/12/10 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2016/12/09 00:00 [pmc-release] AID - PONE-D-16-26886 [pii] AID - 10.1371/journal.pone.0167744 [doi] PST - epublish SO - PLoS One. 2016 Dec 9;11(12):e0167744. doi: 10.1371/journal.pone.0167744. eCollection 2016.