Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart

Significance Remote ischemic preconditioning (IPC) is a phenomenon in which brief cycles of limb ischemia and reperfusion, which can be induced in mice by clamping and unclamping the femoral artery and in human subjects by inflating and deflating a blood pressure cuff, result in protection of the heart against a prolonged episode of ischemia and reperfusion. The underlying mechanism may involve signals transmitted by the nervous system and by secreted factors, including interleukin-10. In this study, we demonstrate that the transcriptional activator hypoxia-inducible factor 1 (HIF-1) is necessary and sufficient for remote IPC in mice and for induction of Il10 gene expression in cultured mouse myocytes. Strategies designed to induce HIF-1 activity may afford cardioprotection in patients undergoing cardiac bypass surgery.