title: Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats.
abstract: OBJECTIVE
  The mechanisms of heart failure remain largely elusive. The present study determined a causative role of DNA methylation in norepinephrine-induced heart hypertrophy and reduced cardiac contractility.
  
  
  RESULTS
  Male adult rats were subjected to norepinephrine infusion for 28 days, some of which were treated with 5-aza-2'-deoxycytidine for the last 6 days of norepinephrine treatment. At the end of the treatment, hearts were isolated and left ventricular morphology and function as well as molecular assessments was determined. Animals receiving chronic norepinephrine infusion showed a sustained increase in blood pressure, heightened global genomic DNA methylation and changes in the expression of subsets of proteins in the left ventricle, left ventricular hypertrophy, and impaired contractility with an increase in the susceptibility to ischaemic injury. Treatment of animals with 5-aza-2'-deoxycytidine for the last 6 days of norepinephrine infusion reversed norepinephrine-induced hypermethylation, corrected protein expression patterns, and rescued the phenotype of heart hypertrophy and failure.
  
  
  CONCLUSIONS
  The findings provide novel evidence of a causative role of increased DNA methylation in programming of heart hypertrophy and reduced cardiac contractility, and suggest potential therapeutic targets of demethylation in the treatment of failing heart and ischaemic heart disease.
authors.affiliation: Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Daliao
authors.initials: D
authors.lastname: Xiao
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Dasgupta
authors.forename: Man
authors.initials: M
authors.lastname: Chen
authors.forename: Kangling
authors.initials: K
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Buchholz
authors.forename: Zhice
authors.initials: Z
authors.lastname: Xu
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009638:Norepinephrine
keywords: Failure; Heart; Hypertrophy; Methylation; Proteomic