Abstract: Objective To test the effect of sRAGE on myocardial apoptosis and STAT3 protein expression with or without STAT3 inhibitor AG490 following ischemia/reperfusion in vivo and in vitro. Methods C57BL/6J mice undergone left anterior descending coronary artery ligation were used as in vivo model and neonatal rat cardiomyocyte subjected to ischemic buffer as an in vitro model. Apoptosis was detected by TUNEL staining and caspase-3 activity. Expression of STAT3/p-STAT3 protein were detected by Western blotting analysis in the presence and absence of the JAK2 inhibitor AG 490. Results In vivo, compared with sham group, the number of TUNEL positive cells and caspase-3 activity were increased by 115% and 120%, and the ratio of p-STAT3/STAT3 was reduced by 50%; sRAGE (100 μg/day) reduced the TUNEL-positive myocytes by 51%, and activity of caspase-3 by 36%, increased the ratio of p-STAT3/STAT3 by 381% followed by I/R. In vitro, compared with control group, the number of TUNEL positive cells and caspase-3 activity increased by 380% and 77%, and the ratio of p-STAT3/STAT3 was reduced by 69%, sRAGE (900 ng/mL) reduced the TUNEL-positive myocytes by 63%, and caspase-3 activity by 33%, increased the ratio of p-STAT3/STAT3 by 243% followed by I/R. The effect of sRAGE reduction on TUNEL-positive myocytes and caspase-3 activity, raise of the ratio of p-STAT3/STAT3 were attenuated by STAT3 inhibitor AG490. Conclusion These results suggest that sRAGE protects cardiomyocytes from apoptosis induced by I/R in vitro and in vivo by activating STAT3.

Key words: sRAGE, myocardial ischemia/reperfusion, apoptosis, STAT3