The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Angiogenesis Is Induced in a Rabbit Model of Hindlimb Ischemia by Naked DNA Encoding an HIF-1α/VP16 Hybrid Transcription Factor
Open accessAbstract
Background —Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that regulates expression of genes involved in O 2 homeostasis, including vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis. We sought to exploit this native adaptive response to hypoxia as a treatment for chronic ischemia. Methods and Results —A hybrid protein consisting of DNA-binding and dimerization domains from the HIF-1α subunit and the transactivation domain from herpes simplex virus VP16 protein was constructed to create a strong, constitutive transcriptional activator. After transfection into HeLa, C6, and Hep3B cells, this chimeric transcription factor was shown to activate expression of the endogenous VEGF gene, as well as several other HIF-1 target genes in vitro. The bioactivity of HIF-1α/VP16 hybrid gene transfer in vivo was examined in a rabbit model of hindlimb ischemia. Administration of HIF-1α/VP16 was associated with significant improvements in calf blood pressure ratio, angiographic score, resting and maximal regional blood flow, and capillary density (all P <0.01). Conclusions —The HIF-1α/VP16 hybrid transcription factor is able to promote significant improvement in perfusion of an ischemic limb. These results confirm the feasibility of a novel approach for therapeutic angiogenesis in which neovascularization may be achieved indirectly by use of a transcriptional regulatory strategy.
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Cited by
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520
Hypoxia-inducible factors and the response to hypoxic stress
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Hypoxia-Inducible Factor-1 (HIF-1)
Ke, Q., & Costa, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027029 · Cited by 1,646
Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology
Semenza, G. L. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)02090-1 · Cited by 930
Molecular basis of the VHL hereditary cancer syndrome
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Metadata
- Authors
- Vincent, K. A., Shyu, K.-G., Luo, Y., Magner, M., Tio, R. A., Jiang, C., Goldberg, M. A., Akita, G. Y., Gregory, R. J., & Isner, J. M.
- Venue
- Circulation
- Published
- 2000-10-31
- Volume
- 102
- Issue
- 18
- Pages
- 2255-2261
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2017902734
- Cited by
- 317
- References
- 38
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Vincent, K. A., Shyu, K.-G., Luo, Y., Magner, M., Tio, R. A., Jiang, C., Goldberg, M. A., Akita, G. Y., Gregory, R. J., & Isner, J. M. (2000). Angiogenesis Is Induced in a Rabbit Model of Hindlimb Ischemia by Naked DNA Encoding an HIF-1α/VP16 Hybrid Transcription Factor. Circulation. https://doi.org/10.1161/01.cir.102.18.2255
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