title: No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.
abstract: OBJECTIVE
  Remote ischemic preconditioning (RIPC) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG). Activation of signal transducer and activator of transcription 5 (STAT5) in left ventricular (LV) myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy.
  
  
  METHODS
  CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation) or placebo (cuff deflated) before skin incision (n = 10/10). Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline) and at early (5-10 min) reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002). Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12) complex, light chain 3 (LC3), parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2)-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion.
  
  
  RESULTS
  Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02). STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05).
  
  
  CONCLUSIONS
  Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.
authors.affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Nilgün
authors.initials: N
authors.lastname: Gedik
authors.affiliation: Klinik für Thorax- und Kardiovaskuläre Chirurgie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Thielmann
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Kottenberg
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
authors.affiliation: Klinik für Thorax- und Kardiovaskuläre Chirurgie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Jakob
authors.affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
mesh_terms: D000368:Aged; D001343:Autophagy; D001026:Coronary Artery Bypass / Q000379:methods*; D005260:Female; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D010766:Phosphorylation; D015424:Reperfusion; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050799:STAT5 Transcription Factor