title: Myocardial release of FKBP12 and increased production of FKBP12.6 in ischemia and reperfusion experimental models.
abstract: BACKGROUND
  Coronary artery occlusion and reperfusion may trigger reversible and irreversible ischemic and reperfusion injury. The primary aim of this study was to evaluate protein release into the myocardium in a porcine model during ischemia and reperfusion to search for clarifying models for reperfusion injury and secondarily to investigate release and production of the immunophilins FKBP12/12.6 in this model and in cell cultures.
  
  
  METHODS
  In a porcine model local myocardial ischemia was induced during 45min followed by 120min of reperfusion. Microdialysis samples from ischemic and non-ischemic areas were analyzed with surface-enhanced laser desorption ionization (SELDI) mass spectrometry (MS) and Western blotting (WB). Myocardial biopsies from areas at risk and control areas were analyzed with reverse transcription polymerase chain reaction (RT-PCR). Myocardial cell cultures from mice (HL-1 cells) were exposed to hypoxia and then analyzed with WB and RT-PCR.
  
  
  RESULTS
  FK binding protein12 (FKBP12), ubiquitin and myoglobin were identified as being released during ischemia and reperfusion in microdialysates. RT-PCR analysis on the biopsies after ischemia revealed a non-significant increase in mRNA expression of FKBP12 and a significant increase in mRNA expression of FKBP12.6. Lysates from HL-1 cells exposed to hypoxia demonstrated increase of FKBP12 and a significant increase in mRNA expression of FKBP12.6.
  
  
  CONCLUSIONS
  In a myocardial ischemic-reperfusion porcine model as well as in hypoxic HL-1 cells, release of FKBP12 and increased production of FKBP12.6 was demonstrated. The findings indicate important mechanisms related to these immunophilins in the reaction to ischemia/hypoxia and reperfusion in the heart.
authors.affiliation: Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. karin.astrom-olsson@vgregion.se
authors.forename: Karin
authors.initials: K
authors.lastname: Aström-Olsson
authors.forename: Lars
authors.initials: L
authors.lastname: Karlsson
authors.forename: Lillemor
authors.initials: L
authors.lastname: Mattsson Hultén
authors.forename: Pia
authors.initials: P
authors.lastname: Davidsson
authors.forename: Vittorio
authors.initials: V
authors.lastname: Mantovani
authors.forename: Chrichan
authors.initials: C
authors.lastname: Månsson
authors.forename: Sven-Olof
authors.initials: SO
authors.lastname: Olofsson
authors.forename: Olov
authors.initials: O
authors.lastname: Wiklund
authors.forename: Lars
authors.initials: L
authors.lastname: Grip
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D013552:Swine; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis*
chemical_list: D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; C403484:tacrolimus binding protein 1B