The Cardioprotection Of Hes1by Crosstalking With Akt/Stat3in Ischemic Postconditioning

Objective: To defined the protective effect of Hes1gene in ischemicpostconditioning (IPost), and explore the endogenous cardioprotective mechanism ofthe Hes1.Methods: Primary cardiac myocytes were suffer from H/R and IPost treatmentfollowing infected with Ad-Hes1and Ad-Hes1-shRNA respectively to up and downregulated the expression of Hes1gene. Primary cardiac myocytes were divided intosix groups of Control, Mock, H/R, H/R+Hes1, IPost, and IPost+Hes1-shRNA. Flowcytometry was used to detect apoptosis, Ψm and ROS, CCK-8was used to assesscell viability, The expression of PTEN, p-Akt/Akt、 p-GSK-3β/GSK-3β andp-Stat3/Stat3were detected by western-blotting.Results: The expression of Hes1gene were increased in myocardial ischemicinjury. The increased expression of Hes1during myocardial H/R can improve cellviability, inhibit apoptosis, stable Ψm, and reduce ROS formation. The Hes1candown-regulat the expression of PTEN, and up-regulated the expression of p-Akt,p-GSK-3β, p-Stat3, simultaneously. However, inhibition of Hes1would weaken Aktand Stat3activity, which abolish the cardioprotective role of IPost.Conclusions: As an endogenous cardioprotective factor, Hes1can reducemyocardial IRI by cross talking with PI3K/Akt, JAK/Stat3signaling, which wouldinhibit mitochondrial permeability transition pore opening and reduce myocardial IRI.