@article {Semenza361, author = {Gregg L Semenza}, title = {Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization}, volume = {64}, number = {2}, pages = {361--363}, year = {2016}, doi = {10.1097/JIM.0000000000000206}, publisher = {BMJ Publishing Group Limited}, 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.}, issn = {1081-5589}, URL = {http://hw-f5-jim.highwire.org/content/64/2/361}, eprint = {http://hw-f5-jim.highwire.org/content/64/2/361.full.pdf}, journal = {Journal of Investigative Medicine} }