Regulation of tissue perfusion in mammals by hypoxia-inducible factor 1

The regulation of tissue perfusion is a major mechanism by which oxygen homeostasis is maintained. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional regulator that mediates adaptive responses to reduced partial pressure of O₂ in all metazoan species. In mammals, HIF-1 promotes angiogenesis, arteriogenesis and vasculogenesis through the production of multiple angiogenic growth factors in ischaemic tissue and by cell-autonomous effects on endothelial cells and bone marrow-derived angiogenic cells. Administration of viral vectors encoding constitutively active forms of the HIF-1α subunit results in increased tissue perfusion in animal models of ischaemic cardiovascular disease.