| AimsCalpain has been implicated in ischemic heart injury.Our recent study showed that inhibition of Calpain can protect heart from injury.Calpastatin is an endogenous Calpain inhibitor of Calpain that can inhibt the activity of Calpain in cells.But the protective effect of Calpastatin is still controversial.we already known that Calpain activation induced endoplasmic reticulum(ER)stress in cardiomyocytes.This study investigated whether over-expression of Calpastatin,provided cardiac protection following myocardial infarction(MI)by inhibiting ER stress/CHOP pathway.Methods and resultsTransgenic mice with Calpastatin over-expression(Tg-CAST)and their wild-type littermates were subjected to MI.Seven days after MI,the mortality was comparable between Tg-CAST and wild-type mice.Echocardiography revealed that myocardial function was improved in TgCAST compared with wild-type mice after MI.Histological analysis showed that over-expression of Calpastatin significantly reduced the diameter of left ventricular cavity and scar area,and prevented cardiac cell death in Tg-CAST versus wild-type MI mice.MI significantly induced CHOP protein expression in wild-type mouse hearts,indicative of ER stress induction,which was abolished in Tg-CAST mice.Furthermore,administration of tauroursodeoxycholic acid(TAUR),an inhibitor of ER stress,abrogated CHOP expression,reduced scar area,prevented cardiac cell death and improved myocardial function after MI.In a rat cardiomyocyte-like H9c2 cell model of oxidant stress,incubation with H2O2 activated Calpain,up-regulated CHOP protein expression and induced apoptosis.All these effects of H2O2 were prevented by Calpain inhibitor PD150606,TAUR or silencing of CHOP.ConclusionTransgenic over-expression of Calpastatin reduces myocardial injury and improves myocardial function in mice after MI.These protective effects of Calpastatin up-regulation may be mediated through ER stress/CHOP pathway. |
