PMID- 28485501 OWN - NLM STAT- MEDLINE DCOM- 20180529 LR - 20200629 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 118 IP - 12 DP - 2017 Dec TI - miR-34a Targets HDAC1-Regulated H3K9 Acetylation on Lipid Accumulation Induced by Homocysteine in Foam Cells. PG - 4617-4627 LID - 10.1002/jcb.26126 [doi] AB - Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR-34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE(-/-) mice fed with high methionine diet, whereas miR-34a expression was inhibited. Over-expression of HDAC1 inhibited H3K9ac level and promoted the accumulation of total cholesterol, free cholesterol, and triglycerides in the foam cells. Furthermore, up-regulation of miR-34a reduced HDAC1 expression and inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and triglycerides (TG) in the foam cells. These data suggest that HDAC1-related H3K9ac plays a key role in Hcy-mediated lipid metabolism disorders, and that miR-34a may be a novel therapeutic target in Hcy-related atherosclerosis. J. Cell. Biochem. 118: 4617-4627, 2017. (c) 2017 Wiley Periodicals, Inc. CI - (c) 2017 Wiley Periodicals, Inc. FAU - Zhao, Qingguo AU - Zhao Q AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Li, Shuqiang AU - Li S AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Li, Nan AU - Li N AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Yang, Xiaoling AU - Yang X AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Ma, Shengchao AU - Ma S AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Yang, Anning AU - Yang A AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Zhang, Hui AU - Zhang H AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Yang, Songhao AU - Yang S AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Mao, Caiyan AU - Mao C AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Xu, Lingbo AU - Xu L AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Gao, Tingting AU - Gao T AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Yang, Xiaoming AU - Yang X AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. FAU - Zhang, Huiping AU - Zhang H AD - Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China. FAU - Jiang, Yideng AU - Jiang Y AUID- ORCID: 0000-0002-4882-5197 AD - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, Yinchuan, Ningxia, China. AD - Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China. LA - eng PT - Journal Article DEP - 20170612 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Apolipoproteins E) RN - 0 (MIRN34a microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Triglycerides) RN - 0LVT1QZ0BA (Homocysteine) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.5.1.98 (Hdac1 protein, mouse) RN - EC 3.5.1.98 (Histone Deacetylase 1) SB - IM MH - Acetylation MH - Animals MH - Apolipoproteins E/deficiency MH - Atherosclerosis/genetics/*metabolism/pathology MH - Cholesterol/genetics/*metabolism MH - Foam Cells/*metabolism/pathology MH - Histone Deacetylase 1/genetics/*metabolism MH - Homocysteine/genetics/*metabolism MH - Male MH - Mice MH - Mice, Knockout MH - MicroRNAs/genetics/*metabolism MH - Triglycerides/genetics/*metabolism OTO - NOTNLM OT - HISTONE ACETYLATION OT - HISTONE DEACETYLASE 1 OT - HYPERHOMOCYSTEINEMIA OT - LIPID ACCUMULATION OT - microRNA EDAT- 2017/05/10 06:00 MHDA- 2018/05/31 06:00 CRDT- 2017/05/10 06:00 PHST- 2017/03/06 00:00 [received] PHST- 2017/05/08 00:00 [accepted] PHST- 2017/05/10 06:00 [pubmed] PHST- 2018/05/31 06:00 [medline] PHST- 2017/05/10 06:00 [entrez] AID - 10.1002/jcb.26126 [doi] PST - ppublish SO - J Cell Biochem. 2017 Dec;118(12):4617-4627. doi: 10.1002/jcb.26126. Epub 2017 Jun 12.