Conclusions
Our data support a causal role for mitochondrial STAT3 activation to mediate cardioprotection through better mitochondrial function.
Objective
We have now in an in situ pig model of regional myocardial ischemia/reperfusion addressed the role of mitochondrial signal transducer and activator of transcription 3 (STAT3).
Results
We demonstrated reduction of infarct size by ischemic postconditioning (26 ± 3% of area at risk versus 38 ± 2% in controls with immediate full reperfusion) along with more markedly increased tyrosine(705) phosphorylation of STAT3 in myocardial biopsies (at 10 minutes reperfusion: 9.2 ± 3.0-fold from baseline versus 6.6 ± 2.9-fold in controls with immediate full reperfusion). Increased tyrosine(705) phosphorylation of STAT3 and better preservation of complex 1 respiration and calcium retention capacity were also present in isolated mitochondria from postconditioned myocardium in vitro. Prior janus kinase/STAT inhibition with AG490 in vivo abrogated the infarct size reduction and the better preservation of mitochondrial function, and the STAT3 inhibitor Stattic in vitro also abrogated better preservation of mitochondrial function. Conclusions: Our data support a causal role for mitochondrial STAT3 activation to mediate cardioprotection through better mitochondrial function.