Abstract 1485: Ischemic Postconditioning’s Protection Is Lost In Aged And Stat3-deficient Mice
The cardioprotection by ischemic preconditioning is lost in aged wildtype (WT) mice and in STAT3-deficient mice (signal transducer and activator of transcription 3). The aim of the present study was to analyze
whether or not ischemic postconditioning (iPo) is effective in aged WT mice hearts, and
whether or not it is dependent on the presence of STAT3.
Young (3 months) and aged (>13 months) C57Bl6/J female mice underwent 30 min of ischemia and 2 h reperfusion (I/R) without or with iPo (3 cycles of 10 s ischemia and 10 s reperfusion (iPo3) or 5 cycles of 5 s ischemia and 5 s reperfusion (iPo5) at the beginning of reperfusion). In young mice hearts, iPo3 and iPo5 reduced the infarct size (IS, % of the area at risk) to a similar extent from 65.8±2.8 (n=11) to 50.7±2.8 (3×10, n=10, p<0.05) and to 49.8±3.8 (5×5, n=10, p<0.05). In contrast, in aged WT hearts IS was similar following I/R and iPo3 (60.1±3.2, n=10 vs. 66.4±3.0, n=7), but was reduced by iPo5 (46.5±4.2, n=7, p<0.05). Western blot analysis on right ventricular protein extracts from aged WT mice hearts indicated a reduction of phosphorylated STAT3 (Ser727) to 72.0±7.6% (n=19, p<0.05) and of total STAT3 to 72.1±5.5% (n=27, p<0.05) of that in young WT mice, which was set as 100% (n=18). In young mice (3 months) with a cardiomyocyte-restricted deletion of STAT3 (STAT3-KO) only iPo3 failed to reduce IS compared to I/R (62.2±3.5, n=5 vs. 64.4±3.1, n=8), whereas the stronger stimulus iPo5 once again significantly reduced IS (55.0±2.8, n=9, p<0.05). In conclusion, lower efficiency of iPO protection against I/R in aged mice hearts was associated with a reduced cardiac expression of STAT3. In line with a crucial role of STAT3 for iPO protection in I/R, STAT3-KO mice displayed also an attenuated susceptibility for iPO mediated protection in I/R. Thus age mediated reduction of cardiac STAT3 expression may contribute to the age-related reduced efficienty of iPo to protect from I/R injury.