title: Aberrant hypermethylation of aldehyde dehydrogenase 2 promoter upstream sequence in rats with experimental myocardial infarction.
abstract: BACKGROUND
  Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role in myocardial protection against ischemia. Downregulation of ALDH2 was evidenced after myocardial infarction and the underlying mechanism is not fully understood. DNA methylation can regulate gene transcription in epigenetic level. We thus hypothesized that DNA methylation may affect ALDH2 expression in myocardial infarction (MI).
  
  
  METHODS
  MI was induced in Sprague-Dawley rats. MI border zone tissues were harvested at 1st week, 2nd week, and 3rd week after MI. Bisulfite sequencing PCR (BSP) was performed to detect the methylation levels of ALDH2 core promoter. Sequenom MassARRAY platform (MassARRAY) was used to examine the methylation levels of ALDH2 promoter upstream sequence. ALDH2 protein and mRNA expression were assayed by Western blot and real-time PCR, respectively.
  
  
  RESULTS
  Compared with Sham group, ALDH2 protein and mRNA expression of MI groups was significantly downregulated. Compared with Sham group, DNA methylation level of CpG sites in ALDH2 promoter upstream sequence was significantly higher in MI groups in a time-dependent manner (CpG1, CpG2, and CpG7, P < 0.01). DNA methylation did not affect ALDH2 core promoter sequence during the progress of MI. No significant difference was detected in DNA methylation level of ALDH2 promoter upstream sequence among MI groups.
  
  
  CONCLUSIONS
  Aberrant hypermethylation of CpG sites in ALDH2 promoter upstream sequence is associated with myocardial ischemia injury and may partly result in ALDH2 downregulation after MI.
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Department of Cardiology, Shandong University, Jinan, Shandong 250012, China.
authors: Peng
authors: P
authors: Wang
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Department of Cardiology, Shandong University, Jinan, Shandong 250012, China.
authors: Cheng
authors: C
authors: Shen
authors: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Lei
authors: L
authors: Diao
authors: Department of Cardiology, Jining Medical College, Jining, Shandong 272067, China.
authors: Zhiyin
authors: Z
authors: Yang
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Fan
authors: F
authors: Fan
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Cong
authors: C
authors: Wang
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Xiangwei
authors: X
authors: Liu
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Xiaolei
authors: X
authors: Sun
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Zhen
authors: Z
authors: Dong
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Hong
authors: H
authors: Zhu
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Xin
authors: X
authors: Ma
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Quan
authors: Q
authors: Cao
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Xiaona
authors: X
authors: Zhao
authors: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Duan
authors: D
authors: Ma
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Yunzeng
authors: Y
authors: Zou
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Kai
authors: K
authors: Hu
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Aijun
authors: A
authors: Sun
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors: Junbo
authors: J
authors: Ge
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D000077209:Decitabine; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000201:enzymology* / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000077209:Decitabine; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D001374:Azacitidine
references: Circ Res. 2008 Apr 25;102(8):873-87
references: 18436802
references: PLoS One. 2010;5(1):e8564
references: 20084101
references: Front Oncol. 2014 May 01;4:80
references: 24822169
references: J Neurochem. 2010 Jul;114(2):520-9
references: 20456012
references: Mol Med Rep. 2014 Jul;10(1):536-42
references: 24736969
references: Curr Pharm Des. 2013;19(27):4865-73
references: 23323620
references: Sci Transl Med. 2011 Nov 2;3(107):107ra111
references: 22049071
references: Biomed Pharmacother. 2011 Dec;65(8):590-3
references: 21123025
references: Cancer Lett. 2011 Dec 1;311(1):85-95
references: 21831520
references: PLoS One. 2014;9(6):e99603
references: 24927503
references: Clin Chem Lab Med. 2013 Feb;51(2):257-70
references: 23072853
references: Int J Epidemiol. 2012 Feb;41(1):106-15
references: 22101166
references: Cardiovasc Res. 2013 Jul 1;99(1):137-45
references: 23519265
references: Int J Cardiol. 2013 Oct 12;168(5):4755-60
references: 23962778
references: J Appl Physiol (1985). 2010 Sep;109(3):916-26
references: 20413423
references: Am J Med Genet A. 2006 May 15;140(10):1069-73
references: 16596676
references: Science. 2008 Sep 12;321(5895):1493-5
references: 18787169
references: PLoS One. 2010;5(3):e9692
references: 20300621
references: Biotechniques. 2013 Oct;55(4):181-97
references: 24107250
references: J Cell Physiol. 2007 Nov;213(2):384-90
references: 17708532
references: Circ Res. 2010 Jun 11;106(11):1681-91
references: 20413785
references: Hum Genet. 2014 Sep;133(9):1093-104
references: 24889829
references: Epigenetics. 2010 Aug 16;5(6):547-56
references: 20543577
references: Eur Heart J. 2011 Apr;32(8):1025-38
references: 20705694
references: Nutr Metab Cardiovasc Dis. 2014 May;24(5):483-8
references: 24418380
references: BMC Med. 2012;10:40
references: 22524197
references: Mol Cell. 2007 Oct 12;28(1):1-13
references: 17936700
references: Cardiovasc Res. 2014 Mar 1;101(3):373-82
references: 24272874
references: Cancer Sci. 2005 Aug;96(8):513-8
references: 16108833
references: Mol Med. 2012;18:785-93
references: 22430940
references: Eur Heart J. 2012 Nov;33(22):2841-8
references: 22511653
references: Basic Res Cardiol. 2005 May;100(3):217-23
references: 15754085
references: Science. 2010 Oct 29;330(6004):612-6
references: 21030644
references: Nature. 2000 May 25;405(6785):482-5
references: 10839546
references: Reproduction. 2013 Dec;146(6):569-79
references: 24051058
references: Hum Mol Genet. 2014 Apr 15;23(8):2176-88
references: 24301681
references: J Lipid Res. 2014 Jul;55(7):1324-30
references: 24711635
references: CA Cancer J Clin. 2010 Nov-Dec;60(6):376-92
references: 20959400
references: BMC Med Genomics. 2012;5:20
references: 22672592