| Title | Regulation of vascularization by hypoxia-inducible factor 1. | | Author(s) | Semenza GL | | Institution | Vascular Program, Institute for Cell Engineering; McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA. | | Source | Ann N Y Acad Sci 2009 Oct.:2-8. | | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19845601 |
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