title: Remote ischemic preconditioning attenuates EGR-1 expression following myocardial ischemia reperfusion injury through activation of the JAK-STAT pathway.
abstract: OBJECTIVE
  Remote ischemic preconditioning (RIPC) protects the myocardium from ischemia/reperfusion (I/R) injury however the molecular pathways involved in cardioprotection are yet to be fully delineated. Transcription factor Early growth response-1 (Egr-1) is a key upstream activator in a variety of cardiovascular diseases. In this study, we elucidated the role of RIPC in modulating the regulation of Egr-1.
  
  
  METHODS
  This study subjected rats to transient blockade of the left anterior descending (LAD) coronary artery with or without prior RIPC of the hind-limb muscle and thereafter excised the heart 24h following surgical intervention. In vitro, rat cardiac myoblast H9c2 cells were exposed to ischemic preconditioning by subjecting them to 3cycles of alternating nitrogen-flushed hypoxia and normoxia. These preconditioned media were added to recipient H9c2 cells which were then subjected to 30min of hypoxia followed by 30min of normoxia to simulate myocardial I/R injury. Thereafter, the effects of RIPC on cell viability, apoptosis and inflammatory markers were assessed.
  
  
  RESULTS
  We showed reduced infarct size and suppressed Egr-1 in the heart of rats when RIPC was administered to the hind leg. In vitro, we showed that RIPC improved cell viability, reduced apoptosis and attenuated Egr-1 in recipient cells.
  
  
  CONCLUSIONS
  Selective inhibition of intracellular signaling pathways confirmed that RIPC increased production of intracellular nitric oxide (NO) and reactive oxygen species (ROS) via activation of the JAK-STAT pathway which then inactivated I/R-induced ERK 1/2 signaling pathways, ultimately leading to the suppression of Egr-1.
authors.affiliation: North Shore Heart Research Foundation, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Electronic address: harshimudaliar@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Mudaliar
authors.affiliation: North Shore Heart Research Foundation, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Rayner
authors.affiliation: North Shore Heart Research Foundation, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Billah
authors.affiliation: North Shore Heart Research Foundation, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Kapoor
authors.affiliation: North Shore Heart Research Foundation, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: W
authors.initials: W
authors.lastname: Lay
authors.affiliation: North Shore Heart Research Foundation, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Dona
authors.affiliation: North Shore Heart Research Foundation, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Bhindi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D032446:Myoblasts; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat
keywords: Cardioprotection; Early growth response-1; JAK-STAT; Myocardial I/R injury; Remote ischemic preconditioning