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.
Original language | English (US) |
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Pages (from-to) | 361-363 |
Number of pages | 3 |
Journal | Journal of investigative medicine : the official publication of the American Federation for Clinical Research |
Volume | 64 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2016 |
Keywords
- angiogenesis
- arteriogenesis
- bronchiolitis obliterans
- critical limb ischemia
- desferrioxamine
- dimethyloxalylglycine
- prolyl hydroxylases
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology