Harnessing the response to tissue hypoxia: HIF-1 alpha and therapeutic angiogenesis

In most cell types a family of transcriptional regulatory proteins termed hypoxia-inducible factors, of which HIF-1 is the most prevalent, mediates the physiologic response to hypoxia. Although much has been learned over the past decade since the discovery of the first HIF family member, the proximal signaling events linking a decline in oxygen concentration to the activation of HIF-dependent signaling are only now being clarified. Activation of HIF-1 in eukaryotes induces expression of many genes that assist in adapting the organism to an environment in which oxygen is limiting, such as of genes involved in new blood vessel formation, including isoforms of vascular endothelial growth factor and angiopoietins, among others. Targeted expression of constitutively active HIF transgenes to ischemic tissues may be beneficial as a form of therapeutic angiogenesis.