CaMKⅡ Plays A Critical Role In Cardiac Protective Effect Of Ischemia-postconditioning

Objective: To explore the effect and the possible mechanisms of Ca²⁺/calmodulin-dependent protein kinase II （CaMK II） in the cardiac protectionof postconditioning（PostC） against myocardial ischemia.Methods: Transgenic mice were divided into3groups （n=20in each group）,including AC3-I（genetic inhibition of CaMKII） group, WT group andAC3-C（transgenic control） group. Using Langendorff perfusion system, weinvestigated the protection role of PostC in ischemia/reperfusion injury inAC3-I, WT and AC3-C mouse hearts. Myocardial infarct size wasdetermined by TTC staining. Myocyte apoptosis was investigated by TUNELstaining. Western blot was employed to detect the content of the p-ERK1/2,ERK1/2, p-Akt, Akt, p-GSK3beta, GSK3beta, p-STAT3and STAT3in hearttissue. Results：AC3I hearts were protected against global ischemia due toenhanced PostC compared to WT and AC3-C hearts. AC3I hearts hadsignificantly smaller myocardial infarction size （p <0.05， respectively） andapoptotic index （p <0.05，respectively） after PostC compared to WT andAC3C hearts after PostC，suggesting that CaMKII inhibition influencemyocyte cells in its role in mediating PostC protection against globalischemia. Furthermore,protein expression of p-ERK1/2, p-Akt, p-GSK3beta,p-STAT3were significantly higher in AC3-I group than in AC3-C groupand WT group （P<0.05, respectively）, whereas the protein expression ofERK1/2, Akt, GSK3beta, STAT3were not different among these3groups（P>0.05, respectively）.Conclusion: CaMKⅡ is a key signaling molecule inischemia-Postconditioning. Transgenic inhibition of CaMMII can enhance thebeneficial effects of PostC possibly by increasing the protein expression ofp-ERK1/2, p-Akt, p-GSK3beta and p-STAT3.