Integrinβ3 Mediates the Protective Effect of Soluble Receptor for Advanced Glycation End-products During Myocardial Ischemia/Reperfusion

Soluble receptor for advanced glycation end-product (sRAGE) was reported to protect myocardial ischemia/reperfusion (I/R) injuries via interacting with AGEs (the ligands of RAGE). Besides, sRAGE was also reported to interact with myocardial cell membranes to protect myocardial I/R injuries. However, the specific molecular of the interaction between sRAGE and myocardial cell membrane is not clearly defined. Integrins were the major adhesion receptors expressed on myocardial cells. The present study showed sRAGE affected the expression of integrinβ3 around integrinβ1 to β5 in I/R treated cardiomyocytes. Consequently, it was supposed that integrinβ3 might be related to the protective effects of sRAGE on myocardial ischemia-reperfusion injuries. The results in this study showed that the protective effects of sRAGE on cardiac function, cardiac infracting size and apoptosis in mice were cancelled by cilengitide (the inhibitor of integrinβ3). Myocardial apoptosis and autophagy decreased by sRAGE in I/R treated cardiomyocytes were showed to be increased by the inhibition of integrinβ3. Mechanistically, the inhibition of integrinβ3 decreased the phosphorylation of Akt and STAT3 but did not affect the phosphorylation of FAK, PTEN, and MAPKs (P38 MAPK, JNK, Erk) in OGD/R and sRAGE treated cardiomyocytes. In addition, the phosphorylation of STAT3 was significantly downregulated by the inhibition of Akt (LY294002,10μM) in OGD/R and sRAGE treated cardiomyocytes. The present study demonstrated integrinβ3 mediated the protective effects of sRAGE on myocardial I/R injuries through Akt-induced STAT3 signaling pathway thus may provide a novel molecular therapy strategy for ameliorating I/R injury.