Hypoxia‐ inducible factor 1 α as a mediator of acute cardioprotection

There is emerging evidence that HIF-1 α activation may contribute to the acute cardioprotective effect elicited by the ‘first window of protection’ or classical IPC. A previous study subjected wild type mice and mice partially deficient in HIF-1 α (HIF-1 α+/−) to IPC (10 min ischemia/5 min reperfusion or two-5 min cycles of ischemia/ reperfusion) immediately prior to 30 min ischemia followed by 30 min reperfusion on the Langendorff-apparatus. As expected in the wildtype hearts IPC resulted in a reduction in MI size, preservation of LV systolic function, and less apoptotic cell death. However, hearts deficient in HIF-1 α were found to be resistant to the beneficial effects of IPC, suggesting that HIF-1 α may act as a mediator of cardioprotection in the acute phase of IPC. Because the mice were partially deficient in HIF-1 α from birth, the mechanism underlying the resistance to IPC must be due to a chronic defect in the signaling pathway. However, a subsequent study has investigated the effects of acute HIF-1 α ablation on IPC protection. A study showed stabilization of HIF-1 α in the cytosol and the nucleus of murine hearts within 3 h of the IPC stimulus. Then it was demonstrated that the intravenous infusion of HIF-1 α siRNA into the left ventricle of IPC-treated hearts maximally suppressed HIF-1 α by 2 h, and this finding was associated with the abrogation of IPC cardioprotection. These findings suggest that the acute phase of IPC is mediated by the stabilization of HIF-1 α which was reported to occur about 30 min following the IPC stimulus.