HIF-1 as a key regulator of O2 delivery and utilization:
- HIF-1 controls oxygen delivery, by regulating angiogenesis and vascular remodeling, as long as oxygen utilization, by regulating glucose metabolism and redox homeostasis;
- HIF-1 activity is induced by hypoxia through changes in HIF-1α mRNA and protein levels in brain, heart, kidney, lung and skeletal muscle;
- HIF-1 functions as a master regulator in angiogenesis and vascular remodeling process because it coordinately regulates the expression of a large number of genes whose protein products play critical roles in mediating vascular responses to hypoxia and ischemia;
- Normal physiological response to reduced tissue perfusion is that the resulting tissue hypoxia induces HIF-1 activity, which activates transcription of genes encoding angiogenic factors. These factors stimulate the remodeling of collateral blood vessels, leading to increased blood flow.
- In addition to promoting O2 delivery, HIF-1 also activates the transcription of genes encoding enzymes, transporters, and mitochondrial proteins that decrease O2 utilization, again functioning as a master regulator to switch cells from oxidative metabolism to glycolytic metabolism;