Regulation of angiogenesis by hypoxia-inducible factors

Abstract

In the years since the identification of hypoxia-inducible factors (HIFs), it has been well established that HIFs regulate angiogenic genes, such as vascular endothelial growth factor. HIFs play essential roles in embryonic vascular development. Recent studies have demonstrated that HIFs can influence the adult vascular system, not only in neovascularization but also in angiogenesis in pathological conditions. In this chapter, oxygen-dependent and novel oxygen-independent regulatory systems of HIF-as are reviewed. Hypoxia-associated factor regulates HIF-1a and HIF-2a reversely. Int6-silencing stabilizes HIF-2a and functional vessel formation. HIFs can be therapeutic targets in both anti-angiogenic and angiogenic therapy. The new findings have implications for the development of therapies for ischemic disease.