title: Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization.
abstract: When tissue perfusion is impaired, the resulting reduction in O2 availability activates hypoxia-inducible factor 1 (HIF-1), which mediates increased transcription of genes encoding multiple angiogenic factors including vascular endothelial growth factor, stromal-derived factor 1, placental growth factor, and angiopoietins, leading to the mobilization of bone marrow-derived angiogenic cells, increased angiogenesis, and arterial remodeling. These HIF- 1-dependent responses are impaired by aging or loss of function mutations at the locus encoding the HIF-1α subunit. in mouse models of limb ischemia and lung transplant rejection, the augmentation of HIF-1 activity by gene therapy or chemical inducers was associated with maintenance of tissue perfusion that prevented limb amputation and allograft rejection, respectively. Thus, targeting HIF-1 may be of therapeutic benefit in these clinical contexts and others in which impaired tissue perfusion plays a role in disease pathogenesis.
authors.affiliation: Institute for Cell Engineering, Department of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry, and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018390:Gene Targeting; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology*; D018919:Neovascularization, Physiologic; D066253:Vascular Remodeling
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: angiogenesis; arteriogenesis; bronchiolitis obliterans; critical limb ischemia; desferrioxamine; dimethyloxalylglycine; prolyl hydroxylases