Hypoxia‐ inducible factor 1 α as a mediator of delayed ischemic preconditioning

It was previously demonstrated that mice partially deficient in HIF-1 α (HIF-1 α⁺/⁻) were resistant to the infarct-limiting effects of intermittent hypoxia and re-oxygenation (the delayed IPC stimulus) administered 24 h earlier, when compared to wild-type mice, suggesting that HIF-1 α was required as a mediator of delayed IPC. In neonatal rat ventricular cardiomyocytes, it has been demonstrated that hypoxic preconditioning (HPC) increased protein expression of HIF-1 α immediately following the preconditioning stimulus, confirming the activation of HIF-1 α in response to the preconditioning stimulus. However, the mechanism through which the IPC stimulus actually stabilizes HIF-1 α is unclear, although a recent experimental study suggests that the IPC-mediated production of mitochondrial ROS may be absent in mice partially deficient in HIF-1 α.