title: High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE(-/-) mice.
abstract: Homocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE(-/-) mice fed high-methionine diet for 20weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The up-regulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
authors.forename: An-Ning
authors.initials: AN
authors.lastname: Yang
authors.affiliation: Prenatal Diagnosis Center of Ningxia Medical University General Hospital, Yinchuan, China; Ningxia Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Yinchuan, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China; Ningxia Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Yinchuan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China; Ningxia Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Yinchuan, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
authors.forename: Guangrong
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Inspection College, Ningxia Medical University, Yinchuan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China; Ningxia Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Yinchuan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Inspection College, Ningxia Medical University, Yinchuan, China.
authors.forename: Sheng-Chao
authors.initials: SC
authors.lastname: Ma
authors.affiliation: Department of Foreign Language Teaching, Ningxia Medical University, Yinchuan, China; Ningxia Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Yinchuan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China; Ningxia Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Yinchuan, China.
authors.forename: Gui-Zhong
authors.initials: GZ
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
authors.forename: Yue-Xia
authors.initials: YX
authors.lastname: Jia
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China; Ningxia Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Yinchuan, China. Electronic address: nyxxgjyd@163.com.
authors.forename: Yi-Deng
authors.initials: YD
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D019175:DNA Methylation; D004032:Diet / Q000009:adverse effects; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005487:Foam Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008715:Methionine / Q000506:poisoning*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; C485852:Dmap1 protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D012097:Repressor Proteins; D002784:Cholesterol; D008715:Methionine
keywords: Atherosclerosis; DNA methylation; Fatty acid-binding protein 4; Foam cell; Homocysteine