vegf hypoxia and angiogenesis
| PAG Title | vegf hypoxia and angiogenesis |
| PAG ID | WAG000413 |
| Type | P |
| Source Link |  BioCarta |
| Publication Reference | NA |
| PAG Description | Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of the VEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mR expression is closely correlated with that of VEGF mR.. The high expression level of HLF mR in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mR. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mR stability by hypoxia. In addition, an interl ribosome entry site (IRES) ensures efficient translation of VEGF mR even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at a post-transcriptiol level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic maligncies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteises, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclol antibodies to VEGF and blockers of the VEGF receptor tyrosine kise pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic maligncies. |
| Species | Homo sapiens |
| nCoCo Score | 3,225 |
| Base PAG ID | WAG000413 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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