title: Remote ischemic preconditioning preserves Connexin 43 phosphorylation in the rat heart in vivo.
abstract: BACKGROUND
  Remote ischemic preconditioning (RIPC) protects the heart from ischemia and reperfusion (I/R) injury. The underlying molecular mechanisms are unclear. It has been demonstrated that Connexin 43 (Cx43) is critically involved in cardioprotective interventions including classical ischemic preconditioning. In the present study we investigated the influence of RIPC on the expression patterns of Cx43 after I/R in the rat heart in vivo.
  
  
  METHODS
  Male Wistar rats were subjected to 35 min regional myocardial ischemia followed by 2 h reperfusion with or without 4 cycles of 5 minutes bilateral hind limb ischemia and reperfusion (RIPC), to RIPC without ischemia or underwent no intervention (Sham). Infarct size was measured by TTC staining. The myocardium was divided into area at risk (AAR) and area not at risk (non AAR). Expression of Cx43-mRNA and protein was analyzed by qPCR and Western Blot analysis, respectively. Localization of Cx43 was visualized by confocal immunofluorescence staining.
  
  
  RESULTS
  RIPC reduced the infarct size (I/R: 73 ± 5% vs.
  34 ± 14%, p < 0.05). Expression of Cx43 mRNA did not differ between groups. I/R caused a strong decrease of relative Cx43 protein expression in the AAR that was partly abolished by RIPC. Furthermore, RIPC decreased the level of ischemia-induced dephosphorylation of Cx43. Confocal immunofluorescence staining showed that I/R caused a loss of the Cx43 signal at the intercalated discs, while the Cx43 signal at the intercalated discs was partly sustained after RIPC.
  
  
  CONCLUSIONS
  Preservation of Cx43 protein expression and phosphorylation after RIPC might protect the rat heart in vivo.
authors.forename: Timo
authors.initials: T
authors.lastname: Brandenburger
authors.forename: Ragnar
authors.initials: R
authors.lastname: Huhn
authors.forename: Andreas
authors.initials: A
authors.lastname: Galas
authors.forename: Benedikt H
authors.initials: BH
authors.lastname: Pannen
authors.forename: Verena
authors.initials: V
authors.lastname: Keitel
authors.forename: Franziska
authors.initials: F
authors.lastname: Barthel
authors.forename: Inge
authors.initials: I
authors.lastname: Bauer
authors.forename: André
authors.initials: A
authors.lastname: Heinen
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D005121:Extremities; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018031:Connexin 43; D011494:Protein Kinases