Myocardial release of FKBP12 and increased production of FKBP12.6 in ischemia and reperfusion experimental models.
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.
Aström-Olsson
Karin
K
Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. karin.astrom-olsson@vgregion.se
Karlsson
Lars
L
Mattsson Hultén
Lillemor
L
Davidsson
Pia
P
Mantovani
Vittorio
V
Månsson
Chrichan
C
Olofsson
Sven-Olof
SO
Wiklund
Olov
O
Grip
Lars
L
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*
D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; C403484:tacrolimus binding protein 1B