Erythropoietin protects rats with heart failure in hypothermia by activating PI3K/Akt pathway and upregulating the expression of HSP70

AIM:To investigate the effect oferythropoietin (EPO) on the rats with heart failure (HF) in hypothermia and to explore its underlying mechanism.METHODS:The Sprague-Dawley rats (n=80) were randomly divided into five groups:control group (CON group),HF in low-temperature group (HFLT group),HF in normal temperature group (HFNT group),HF with EPO in low temperature group (HFLT+EPO group),and HF with EPO and LY2940002 in low temperature group (HFLT+EPO+LY group).All rats were housed in artifitial climate chamber.The animals in CON,HFLT,HFLT+EPO and HFLT+EPO+LY groups were under the low-temperature environment,while those in HFNT group were under normal temperature.The heart function was evaluated by echocardiography.The rats were then executed and the hearts were harvested.The apoptosis of myocytes was assessed by TUNEL method.The mRNA expression of Fas and PI3K was detected by fluorescence quantitative PCR (qPCR) and the protein levels of HSP70,Akt and p-Akt in the myocardial tissues were determined by Western blot.RESULTS:The rat cardiac functions in HFLT group were significantly deteriorated compared with HFNT group.The cardiac functions in HFLT+EPO group were improved compared with HFLT group.The cardiac functions in HFLT+EPO+LY group were significantly pejorated compared with HFLT+EPO group.The apoptotic index of the myocardium in HFLT group and HFNT group was significantly higher than that in CON group (P<0.01).The apoptotic index of the myocardium in HFLT group was significantly higher than that in HFNT group (P<0.05).The apoptotic index of the myocardium in HFLT+EPO group was significantly lower than that in HFLT group (P<0.01).The mRNA expression of Fas in HFLT group was significantly higher than that in HFNT group,and no obvious difference of the mRNA expression level of PI3K between HFLT group and HFNT group was observed.The mRNA expression of PI3K in HFLT+EPO group was significantly lower than that in HFLT group and HFLT+EPO+LY group (P<0.05),and that in HFLT+EPO group was significantly higher than that in HFLT group and HFLT+EPO+LY group (P<0.05). The protein levels of p-Akt and HSP70 in HFLT+EPO group was also higher than those in HFLT group and HFLT+EPO+LY group (P<0.05),and no obvious difference of the protein levels of p-Akt and HSP70 in CON,HFLT and HFNT groups was found.The protein level of Akt had no significant difference in each group.CONCLUSION:The pathway of PI3K/Akt may be one of the cardioprotective ways of EPO.EPO activates the PI3K/Akt pathway,upregulates the experssion of HSP70(an endogenous protective factor) and inhibits the apoptosis,thus protecting the cardiac functions in the rats with HF in hypothermia.