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Gene Review

Vegfa  -  vascular endothelial growth factor A

Rattus norvegicus

Synonyms: VEGF-A, VEGF164, VPF, Vascular endothelial growth factor A, Vascular permeability factor, ...
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Disease relevance of Vegfa

  • Because we have previously demonstrated that hypoxia (3% O2) can enhance VSMC proliferation induced by VEGF-A through Flt-1 receptor upregulation, the effects of hypoxia on the response of VSMCs to MCP-1 were investigated [1].
  • Increasing fetal lung distension by tracheal occlusion (TO) accelerated the normal maturational pattern of VEGF-A isoforms and increased VEGF-A protein; decreasing fetal lung distension by congenital diaphragmatic hernia (CDH) retarded the normal developmental pattern and decreased VEGF-A protein [2].
  • 17alpha-E(2), a weak estrogen exhibited both agonistic and antagonistic effects, and caused a time- and dose-dependent induction of VEGF-A mRNA expression in GH3 rat pituitary tumor cells [3].
  • Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is highly expressed in the myocardium under various stimuli including hypoxia and ischemia [4].
  • VEGF, which is also known as vascular permeability factor (VPF), is a recently identified specific mitogen for endothelial cells, and has been paid much attention for the critical participation in the physiological and pathological angiogenesis/vasculogenesis in retinas [5].

High impact information on Vegfa

  • On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats [6].
  • By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset [6].
  • VPF caused normal venules to leak ferritin, and, as predicted by our hypothesis, ferritin extravasated by way of VVOs, just as in hyperpermeable tumor microvessels [7].
  • To explain these findings, we hypothesized that VPF increased the permeability of tumor blood vessels by increasing VVO function and that the VVOs of normal venules were relatively impermeable in the absence of VPF stimulation [7].
  • In situ hybridization revealed that greatly increased amounts of VPF mRNA were expressed by keratinocytes, initially those at the wound edge, and, at later intervals, keratinocytes that migrated to cover the wound surface; occasional mononuclear cells also expressed VPF mRNA [8].

Chemical compound and disease context of Vegfa


Biological context of Vegfa


Anatomical context of Vegfa

  • VEGF-A protein was expressed in alveolar epithelium (type I and II cells) and interstitium [2].
  • The VEGFA signaling inhibitors SU1498 (40 microM) and VEGFR-TKI (8 microM) inhibited cord formation in E13 testis cultures with 90% reduced vascular density (P<0.01) in VEGFR-TKI-treated organs [10].
  • Endogenous VEGF-A is responsible for mitogenic effects of MCP-1 on vascular smooth muscle cells [1].
  • VEGFA protein was localized to Sertoli cells at cord formation and KDR to germ and interstitial cells [10].
  • Studies also demonstrate that the VEGF-A protein, induced by 2-ME2, is functionally active and upregulates the proliferation of adjacent endothelial cells [11].

Associations of Vegfa with chemical compounds


Regulatory relationships of Vegfa


Other interactions of Vegfa

  • Glomeruli are capable of healing microaneurysms, and the mechanism involves basic fibroblast growth factor- and VPF/VEGF-mediated endothelial proliferative responses [16].
  • Three weeks after monocrotaline (MCT) treatment, Fisher 344 rats were randomized to receive a total of either 1.5 x 10(6) syngeneic fibroblasts (FB) transfected with vascular endothelial growth factor A (VEGF), endothelial NO synthase (eNOS), or null-plasmid transfected FBs [17].
  • Microarray analysis detected maximal mRNA expression for a wide variety of angiogenic factors including angiopoietin 1 and 2, both Tie receptors, VEGF-A and -D, VEGFR2, and neuropilin 1 [18].
  • Correspondingly, the VEGF-C-specific receptor flt-4 and the VEGF-A receptors flt-1 and flk-1 were up-regulated in a temporal sequence similar to that of their agonist proteins in the cortical ring lesion and the region at risk [19].
  • Intensive TGF-beta 1 immuno-reactivity was induced immediately, whereas a lag period was observed for VEGF-A [20].

Analytical, diagnostic and therapeutic context of Vegfa

  • Expression of TGF-beta 1 and VEGF-A mRNA in the defect tissues was also significantly increased (P<0.05) after ESW treatment as determined by RT-PCR [20].
  • Vascular endothelial growth factor-A and -C protein up-regulation and early angiogenesis in a rat photothrombotic ring stroke model with spontaneous reperfusion [19].
  • Thus Fgf and Vegf were induced concomitantly with the decrease in the staining for endothelial AP by 20 Gy X irradiation, which also caused microeffects as indicated by TUNEL staining of many nuclei at 1 h postirradiation [21].
  • Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery [6].
  • METHODS: VEGF-A and VEGFR2 were localized using immunocytochemistry [22].


  1. Endogenous VEGF-A is responsible for mitogenic effects of MCP-1 on vascular smooth muscle cells. Parenti, A., Bellik, L., Brogelli, L., Filippi, S., Ledda, F. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  2. Changes in fetal lung distension alter expression of vascular endothelial growth factor and its isoforms in developing rat lung. Hara, A., Chapin, C.J., Ertsey, R., Kitterman, J.A. Pediatr. Res. (2005) [Pubmed]
  3. 17alpha-estradiol-induced VEGF-A expression in rat pituitary tumor cells is mediated through ER independent but PI3K-Akt dependent signaling pathway. Banerjee, S., Saxena, N., Sengupta, K., Banerjee, S.K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  4. Lipopolysaccharide augments expression and secretion of vascular endothelial growth factor in rat ventricular myocytes. Sugishita, Y., Shimizu, T., Yao, A., Kinugawa, K., Nojiri, T., Harada, K., Matsui, H., Nagai, R., Takahashi, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  5. Endothelial and glial cell interaction in diabetic retinopathy via the function of vascular endothelial growth factor (VEGF). Sueishi, K., Hata, Y., Murata, T., Nakagawa, K., Ishibashi, T., Inomata, H. Polish journal of pharmacology. (1996) [Pubmed]
  6. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Storkebaum, E., Lambrechts, D., Dewerchin, M., Moreno-Murciano, M.P., Appelmans, S., Oh, H., Van Damme, P., Rutten, B., Man, W.Y., De Mol, M., Wyns, S., Manka, D., Vermeulen, K., Van Den Bosch, L., Mertens, N., Schmitz, C., Robberecht, W., Conway, E.M., Collen, D., Moons, L., Carmeliet, P. Nat. Neurosci. (2005) [Pubmed]
  7. Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin. Feng, D., Nagy, J.A., Hipp, J., Dvorak, H.F., Dvorak, A.M. J. Exp. Med. (1996) [Pubmed]
  8. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. Brown, L.F., Yeo, K.T., Berse, B., Yeo, T.K., Senger, D.R., Dvorak, H.F., van de Water, L. J. Exp. Med. (1992) [Pubmed]
  9. Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. Heiss, J.D., Papavassiliou, E., Merrill, M.J., Nieman, L., Knightly, J.J., Walbridge, S., Edwards, N.A., Oldfield, E.H. J. Clin. Invest. (1996) [Pubmed]
  10. Vascular endothelial growth factor and kinase domain region receptor are involved in both seminiferous cord formation and vascular development during testis morphogenesis in the rat. Bott, R.C., McFee, R.M., Clopton, D.T., Toombs, C., Cupp, A.S. Biol. Reprod. (2006) [Pubmed]
  11. 2-Methoxyestradiol exhibits a biphasic effect on VEGF-A in tumor cells and upregulation is mediated through ER-alpha: a possible signaling pathway associated with the impact of 2-ME2 on proliferative cells. Banerjee, S.N., Sengupta, K., Banerjee, S., Saxena, N.K., Banerjee, S.K. Neoplasia (2003) [Pubmed]
  12. Recombinant AAV vector encoding human VEGF165 enhances wound healing. Deodato, B., Arsic, N., Zentilin, L., Galeano, M., Santoro, D., Torre, V., Altavilla, D., Valdembri, D., Bussolino, F., Squadrito, F., Giacca, M. Gene Ther. (2002) [Pubmed]
  13. Vascular endothelial growth factor mediates vasogenic edema in acute lead encephalopathy. Hossain, M.A., Russell, J.C., Miknyoczki, S., Ruggeri, B., Lal, B., Laterra, J. Ann. Neurol. (2004) [Pubmed]
  14. Depleted dopamine in gastric cancer tissues: dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis. Chakroborty, D., Sarkar, C., Mitra, R.B., Banerjee, S., Dasgupta, P.S., Basu, S. Clin. Cancer Res. (2004) [Pubmed]
  15. Endothelin-1 down-regulates the expression of vascular endothelial growth factor-A associated with osteoprogenitor proliferation and differentiation. Veillette, C.J., von Schroeder, H.P. Bone (2004) [Pubmed]
  16. Participation of glomerular endothelial cells in the capillary repair of glomerulonephritis. Iruela-Arispe, L., Gordon, K., Hugo, C., Duijvestijn, A.M., Claffey, K.P., Reilly, M., Couser, W.G., Alpers, C.E., Johnson, R.J. Am. J. Pathol. (1995) [Pubmed]
  17. Microvascular regeneration in established pulmonary hypertension by angiogenic gene transfer. Zhao, Y.D., Courtman, D.W., Ng, D.S., Robb, M.J., Deng, Y.P., Trogadis, J., Han, R.N., Stewart, D.J. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  18. Expression of angiogenic factors during distraction osteogenesis. Pacicca, D.M., Patel, N., Lee, C., Salisbury, K., Lehmann, W., Carvalho, R., Gerstenfeld, L.C., Einhorn, T.A. Bone (2003) [Pubmed]
  19. Vascular endothelial growth factor-A and -C protein up-regulation and early angiogenesis in a rat photothrombotic ring stroke model with spontaneous reperfusion. Gu, W., Brännström, T., Jiang, W., Bergh, A., Wester, P. Acta Neuropathol. (2001) [Pubmed]
  20. Recruitment of mesenchymal stem cells and expression of TGF-beta 1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats. Chen, Y.J., Wurtz, T., Wang, C.J., Kuo, Y.R., Yang, K.D., Huang, H.C., Wang, F.S. J. Orthop. Res. (2004) [Pubmed]
  21. Induction of growth factors in rat cardiac tissue by X irradiation. Gao, M., Shirato, H., Miyasaka, K., Kuwabara, M., Koyama, T. Radiat. Res. (2000) [Pubmed]
  22. Vascular endothelial growth factor expression and signaling in the lens. Shui, Y.B., Wang, X., Hu, J.S., Wang, S.P., Garcia, C.M., Potts, J.D., Sharma, Y., Beebe, D.C. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
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