title: Restoration of altered microRNA expression in the ischemic heart with resveratrol.
abstract: BACKGROUND
  Resveratrol, a constituent of red wine, is important for cardioprotection. MicroRNAs are known regulators for genes involved in resveratrol-mediated cardiac remodeling and the regulatory pathway involving microRNA has not been studied so far.
  
  
  METHODS
  We explored the cardioprotection by resveratrol in ischemia/reperfusion model of rat and determined cardiac functions. miRNA profile was determined from isolated RNA using quantitative Real-time PCR based array. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches.
  
  
  RESULTS
  Cardioprotection by resveratrol and its derivative in ischemia/reperfusion [I/R] rat model was examined with miRNA expression profile. Unique expression pattern were found for each sample, particularly with resveratrol [pure compound] and longevinex [commercial resveratrol formulation] pretreated hearts. Longevinex and resveratrol pretreatment modulates the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 25 miRNAs, some of them, such as miR-21 were previously implicated in cardiac remodeling. The target genes for the differentially expressed miRNA include genes of various molecular function such as metal ion binding, sodium-potassium ion, transcription factors, which may play key role in reducing I/R injury.
  
  
  CONCLUSIONS
  Rats pretreated with resveratrol for 3 weeks leads to significant cardioprotection against ischemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or longevinex. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R mice.
authors.affiliation: Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Partha
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Subhendu
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Kaimul
authors.initials: K
authors.lastname: Ahsan
authors.forename: Angshuman
authors.initials: A
authors.lastname: Bagchi
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Das
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012984:Software; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D035683:MicroRNAs; D013267:Stilbenes; D000077185:Resveratrol