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- Title
Regulation of vascularization by hypoxia-inducible factor 1.
- Authors
Semenza, Gregg L
- Abstract
Vascularization and vascular remodeling represent critical adaptive responses to tissue hypoxia that are mediated by hypoxia-inducible factor 1 (HIF-1). In patients with peripheral arterial disease, these responses are impaired by aging and diabetes, leading to critical limb ischemia and amputation. Intramuscular injection of an adenovirus encoding a constitutively active form of the HIF-1alpha subunit (CA5) increases the recovery of blood flow following femoral artery ligation in a mouse model of age-dependent critical limb ischemia. Intradermal injection of a plasmid encoding CA5 promotes healing of cutaneous wounds in a mouse model of diabetes. In cancer, vascularization is required for tumors to grow beyond microscopic size, a process that involves HIF-1-dependent production of angiogenic growth factors. Daily treatment of prostate cancer xenograft-bearing mice with low-dose anthracycline (doxorubicin or daunorubicin) chemotherapy inhibits HIF-1 DNA-binding activity, HIF-1-dependent expression of angiogenic growth factors, mobilization of circulating angiogenic cells, and tumor vascularization, thereby arresting tumor growth.
- Publication
Annals of the New York Academy of Sciences, 2009, Vol 1177, p2
- ISSN
1749-6632
- Publication type
Journal Article
- DOI
10.1111/j.1749-6632.2009.05032.x