title: Alcohol-induced histone H3K9 hyperacetylation and cardiac hypertrophy are reversed by a histone acetylases inhibitor anacardic acid in developing murine hearts.
abstract: BACKGROUND
  The expression of cardiac genes is precisely regulated, and any perturbation may cause developmental defects. In a previous study, we demonstrated that alcohol consumption during pregnancy could lead to uncontrolled expressions of cardiac genes and eventually result in cardiac dysplasia. However, the underlying mechanisms remain unclear. In the present study, we have investigated the alcohol-induced cardiac hypertrophy and its potential mechanisms. Furthermore, the protective effect of anacardic acid against the alcohol-induced cardiac hypertrophy has been explored in experimental mice.
  
  
  RESULTS
  C57BL/6 pregnant mice were gavaged with 56% ethanol or saline and the hearts of their fetus were collected for analysis. Binding of p300, CBP, PCAF, SRC1, except GCN5, were increased to the NKX2.5 promoter in fetal mouse hearts exposed to alcohol. Increased acetylation of H3K9 and increased mRNA expression of NKX2.5, β-MHC and Cx43 were observed in the same samples. Treatment with a pan-acetylase inhibitor, anacardic acid, reduced the binding affinity of p300 and PCAF to the NKX2.5, β-MHC, Cx43 promoters and attenuated H3K9 hyperacetylation. Interestingly, anacardic acid down-regulated over-expression of these cardiac genes induced by alcohol and ultimately attenuated ethanol-induced cardiac hypertrophy in fetal mice.
  
  
  CONCLUSIONS
  Our results indicate that alcohol exposure during pregnancy could lead to fetal cardiac hypertrophy. The over-expression of NKX2.5, β-MHC, Cx43 mediated by p300 and PCAF may be critical mechanisms of alcohol-induced cardiac hypertrophy. Anacardic acid can down-regulate the over-expression of cardiac genes and reverse cardiac hypertrophy caused by alcohol treatment in pregnant mice, suggesting it could be a potential therapeutic agent for the treatment of cardiac hypertrophy.
authors: Heart Center, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Key Laboratory of Pediatrics in Chongqing, Chongqing, PR China.
authors: Chang
authors: C
authors: Peng
authors: Heart Center, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Key Laboratory of Pediatrics in Chongqing, Chongqing, PR China.
authors: Weihua
authors: W
authors: Zhang
authors: Heart Center, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Key Laboratory of Pediatrics in Chongqing, Chongqing, PR China.
authors: Weian
authors: W
authors: Zhao
authors: Key Laboratory of Pediatrics in Chongqing, Chongqing, PR China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, PR China.
authors: Jing
authors: J
authors: Zhu
authors: Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, United States.
authors: Xupei
authors: X
authors: Huang
authors: Heart Center, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. Electronic address: jietian@cqmu.edu.cn.
authors: Jie
authors: J
authors: Tian
mesh_terms: D000107:Acetylation / Q000187:drug effects; D048729:Anacardic Acids / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000196:embryology / Q000473:pathology / Q000517:prevention & control; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D006321:Heart / Q000196:embryology; D006657:Histones / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D048729:Anacardic Acids; D000431:Ethanol; D006657:Histones; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C088115:anacardic acid
keywords: Alcohol; Anacardic acid; Cardiac hypertrophy; Histone acetylases