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Review
. 2016 Feb;64(2):361-3.
doi: 10.1097/JIM.0000000000000206. Epub 2016 Jan 11.

Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization

Gregg L Semenza  1
Affiliations
Review

Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization

Gregg L Semenza. J Investig Med. 2016 Feb.

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.

Keywords: angiogenesis; arteriogenesis; bronchiolitis obliterans; critical limb ischemia; desferrioxamine; dimethyloxalylglycine; prolyl hydroxylases.

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References

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