PostC not only reduces infarction PF01367338 size but also limits apoptosis after reperfusion. Recent studies reported that PostC affords persistent infarction size reduction after prolonged reperfusion in both canine models and humans. But they did not distinguish whether this long term cardioprotection was a continued effect of the early phase or an independent effect. The present results suggested that PostC could limit myocardial apoptosis after reperfusion. Bcl 2 levels were significantly up regulated by PostC. Interestingly, there was an increase in Bcl 2 levels between 2 and 24 hours after reperfusion in PostC groups. This indicated that PostC may reduce myocardial apoptosis during pro longed reperfusion via up regulated anti apoptotic fac tors such as Bcl 2.

Further study focus on other apoptosis associated proteins such as Bcl x, Inhibitors,Modulators,Libraries BAD and BAX may be helpful to define the long term benefit of PostC. The anti apoptotic effects of the JAK2 STAT3 signal ing pathway have been shown by several studies in tumors. Several apoptosis related protein genes, such as Bcl 2 and Bcl xl, have been identified as target genes of STAT3. Many studies have demonstrated that ischemic preconditioning upregulates COX 2 and iNOS at 24 hours after intervention, which is dependent on transcriptional regulation by the JAK STAT pathway. The present results showed that PostC signifi cantly activated STAT3 after reperfusion and AG490 attenuated the anti apoptotic effect of PostC. Elevation of Bcl 2 after reperfusion required STAT3 activation which indicated that PostC may afford a persistent anti apoptotic effect via a JAK2 STAT3 Bcl 2 pathway.

Activation of the PI3K/Akt pathway prevents cardiac myocyte apoptosis and protects the myocardium from I/ R injury. Furthermore, as the major component of the RISK pathway, the PI3K/Akt pathway has been shown to play a crucial role in PostC. Goodman et al. demonstrated that JAK STAT signaling may provide upstream initiation Inhibitors,Modulators,Libraries of RISK pathway signaling via PI3K Akt Inhibitors,Modulators,Libraries activation, and JAK STAT signaling is insufficient on its own to provide cardioprotection following PostC without subsequent RISK activation. In accordance with this, the present study showed that JAK2 signaling regulated the activa tion of the PI3K/Akt pathway in PostC.

Blocking the PI3K/Akt pathway attenuated the cardioprotection of Background Multiple studies have shown that ischemic precondition ing, defined as one or more Inhibitors,Modulators,Libraries brief ischemic insult, confers organ protection from I/R injury. Although IPC has shown protective effects against I/R injury, its utilization as clinical strategy is largely limited because the onset of ischemia is difficult Inhibitors,Modulators,Libraries to be predicted. However, the onset of reperfusion is more predictable. Recently, a new selleckbio strategy, named ischemic postcondition ing, was described by Zhao et al and showed promising results for cardiac reperfusion injury.