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Gene Review

VEGFA  -  vascular endothelial growth factor A

Homo sapiens

Synonyms: MVCD1, VEGF, VEGF-A, VPF, Vascular endothelial growth factor A, ...
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Disease relevance of VEGFA


Psychiatry related information on VEGFA

  • These results indicated that Id plays a crucial role in VEGF-induced signals of endothelial cells by causing activation and potentiation of angiogenic processes [9].
  • In a gain of function transgene-like approach the retroviral expression vector RCAS was used to increase the level of quail VEGF during critical periods of avian limb bud growth and morphogenesis [10].
  • Haplotype analysis in VEGF gene and increased risk of Alzheimer's disease [11].
  • RESULTS: When hypertensive patients were compared with the controls, there was no statistically significant difference in total physical activity score using the Baecke questionnaire although plasma VEGF and vWf levels were higher, but sFlt-1 levels and FMD lower (all P < 0.001) [12].
  • RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08+/-16.23 vessels/HP vs 80.00+/-26.27 vessels/HP, 0.0538+/-0.0165 vs 0.7373+/-0.1297, respectively, P<0.05) [13].

High impact information on VEGFA


Chemical compound and disease context of VEGFA


Biological context of VEGFA


Anatomical context of VEGFA


Associations of VEGFA with chemical compounds


Physical interactions of VEGFA

  • Of the synthetic peptides corresponding to selected clones tested to determine their inhibitory activity, ATWLPPR completely abolished VEGF binding to cell-displayed KDR [35].
  • NRP2 specifically binds VEGF-A and VEGF-C, although the biological relevance of these interactions in human endothelial cells is poorly understood [36].
  • Moreover, we demonstrated by RNA affinity purification as well as by ribonucleoprotein complexes immunoprecipitation, that PAIP2 interacts with VEGF mRNA in vivo [37].
  • STAT3 and hypoxia-inducible factor (HIF)-1alpha bind simultaneously to the VEGF promoter, where they form a molecular complex with the transcription coactivators CBP/p300 and Ref-1/APE [38].
  • CONCLUSIONS: Exogenous VEGF interacts with VEGFR-1 and VEGFR-2 on the surface and regulates the proliferation of injured alveolar lining epithelial cells in an autocrine or paracrine fashion [39].

Enzymatic interactions of VEGFA


Co-localisations of VEGFA


Regulatory relationships of VEGFA


Other interactions of VEGFA

  • Our results provide an insight into hypoxia-triggered intracellular signalling, define VEGF as a new downstream target for c-SRC, and suggest a role for c-SRc in promoting angiogenesis [25].
  • In venous and arterial endothelial cells, TNF-alpha potently reduced mRNA transcripts of the two VEGF receptors (KDR/flk-1 and flt-1) in a dose- and time-dependent fashion [33].
  • The formation of ascites was directly associated with expression of VEGF/ VPF, and survival was inversely associated with expression of IL-8 [54].
  • The coagulation factor domains alone are necessary and sufficient for binding of the Sema III immunoglobulin- (Ig-) basic domain and the unrelated ligand, vascular endothelial growth factor (VEGF) [55].
  • These findings indicate that GAG modification of NRP1 plays a critical role in modulating VEGF signaling, and may provide new insights into physiological and pathological angiogenesis [56].

Analytical, diagnostic and therapeutic context of VEGFA


  1. Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Mizukami, Y., Jo, W.S., Duerr, E.M., Gala, M., Li, J., Zhang, X., Zimmer, M.A., Iliopoulos, O., Zukerberg, L.R., Kohgo, Y., Lynch, M.P., Rueda, B.R., Chung, D.C. Nat. Med. (2005) [Pubmed]
  2. Angiopoietin-1 protects the adult vasculature against plasma leakage. Thurston, G., Rudge, J.S., Ioffe, E., Zhou, H., Ross, L., Croll, S.D., Glazer, N., Holash, J., McDonald, D.M., Yancopoulos, G.D. Nat. Med. (2000) [Pubmed]
  3. The biology of VEGF and its receptors. Ferrara, N., Gerber, H.P., LeCouter, J. Nat. Med. (2003) [Pubmed]
  4. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Nishijima, K., Ng, Y.S., Zhong, L., Bradley, J., Schubert, W., Jo, N., Akita, J., Samuelsson, S.J., Robinson, G.S., Adamis, A.P., Shima, D.T. Am. J. Pathol. (2007) [Pubmed]
  5. Interstitial vascular rarefaction and reduced VEGF-A expression in human diabetic nephropathy. Lindenmeyer, M.T., Kretzler, M., Boucherot, A., Berra, S., Yasuda, Y., Henger, A., Eichinger, F., Gaiser, S., Schmid, H., Rastaldi, M.P., Schrier, R.W., Schlöndorff, D., Cohen, C.D. J. Am. Soc. Nephrol. (2007) [Pubmed]
  6. Blocking vascular endothelial growth factor-A inhibits the growth of pituitary adenomas and lowers serum prolactin level in a mouse model of multiple endocrine neoplasia type 1. Korsisaari, N., Ross, J., Wu, X., Kowanetz, M., Pal, N., Hall, L., Eastham-Anderson, J., Forrest, W.F., Van Bruggen, N., Peale, F.V., Ferrara, N. Clin. Cancer Res. (2008) [Pubmed]
  7. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Burstein, H.J., Chen, Y.H., Parker, L.M., Savoie, J., Younger, J., Kuter, I., Ryan, P.D., Garber, J.E., Chen, H., Campos, S.M., Shulman, L.N., Harris, L.N., Gelman, R., Winer, E.P. Clin. Cancer Res. (2008) [Pubmed]
  8. Hypoxia-inducible factor is expressed in giant cell tumour of bone and mediates paracrine effects of hypoxia on monocyte-osteoclast differentiation via induction of VEGF. Knowles, H.J., Athanasou, N.A. J. Pathol. (2008) [Pubmed]
  9. Crucial role of inhibitor of DNA binding/differentiation in the vascular endothelial growth factor-induced activation and angiogenic processes of human endothelial cells. Sakurai, D., Tsuchiya, N., Yamaguchi, A., Okaji, Y., Tsuno, N.H., Kobata, T., Takahashi, K., Tokunaga, K. J. Immunol. (2004) [Pubmed]
  10. Overexpression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation. Flamme, I., von Reutern, M., Drexler, H.C., Syed-Ali, S., Risau, W. Dev. Biol. (1995) [Pubmed]
  11. Haplotype analysis in VEGF gene and increased risk of Alzheimer's disease. Saleheen, D. Ann. Neurol. (2005) [Pubmed]
  12. Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Felmeden, D.C., Spencer, C.G., Blann, A.D., Beevers, D.G., Lip, G.Y. J. Intern. Med. (2003) [Pubmed]
  13. Effects of thalidomide on angiogenesis and tumor growth and metastasis of human hepatocellular carcinoma in nude mice. Zhang, Z.L., Liu, Z.S., Sun, Q. World J. Gastroenterol. (2005) [Pubmed]
  14. Recent progress in the management of advanced renal cell carcinoma. Garcia, J.A., Rini, B.I. CA: a cancer journal for clinicians (2007) [Pubmed]
  15. Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Brutsaert, D.L. Physiol. Rev. (2003) [Pubmed]
  16. Vascular growth factors and lymphangiogenesis. Jussila, L., Alitalo, K. Physiol. Rev. (2002) [Pubmed]
  17. An SDF-1 trap for myeloid cells stimulates angiogenesis. Ruiz de Almodovar, C., Luttun, A., Carmeliet, P. Cell (2006) [Pubmed]
  18. Sculpting heart valves with NFATc and VEGF. Lambrechts, D., Carmeliet, P. Cell (2004) [Pubmed]
  19. Induction of hypoxia-inducible factor-1, erythropoietin, vascular endothelial growth factor, and glucose transporter-1 by hypoxia: evidence against a regulatory role for Src kinase. Gleadle, J.M., Ratcliffe, P.J. Blood (1997) [Pubmed]
  20. Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Hyder, S.M., Nawaz, Z., Chiappetta, C., Stancel, G.M. Cancer Res. (2000) [Pubmed]
  21. Potentiation of the antiangiogenic ability of linomide by androgen ablation involves down-regulation of vascular endothelial growth factor in human androgen-responsive prostatic cancers. Joseph, I.B., Isaacs, J.T. Cancer Res. (1997) [Pubmed]
  22. Vascular endothelial growth factor contributes to prostate cancer-mediated osteoblastic activity. Kitagawa, Y., Dai, J., Zhang, J., Keller, J.M., Nor, J., Yao, Z., Keller, E.T. Cancer Res. (2005) [Pubmed]
  23. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Wedge, S.R., Ogilvie, D.J., Dukes, M., Kendrew, J., Chester, R., Jackson, J.A., Boffey, S.J., Valentine, P.J., Curwen, J.O., Musgrove, H.L., Graham, G.A., Hughes, G.D., Thomas, A.P., Stokes, E.S., Curry, B., Richmond, G.H., Wadsworth, P.F., Bigley, A.L., Hennequin, L.F. Cancer Res. (2002) [Pubmed]
  24. The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Basu, S., Nagy, J.A., Pal, S., Vasile, E., Eckelhoefer, I.A., Bliss, V.S., Manseau, E.J., Dasgupta, P.S., Dvorak, H.F., Mukhopadhyay, D. Nat. Med. (2001) [Pubmed]
  25. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Mukhopadhyay, D., Tsiokas, L., Zhou, X.M., Foster, D., Brugge, J.S., Sukhatme, V.P. Nature (1995) [Pubmed]
  26. VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Gerber, H.P., Malik, A.K., Solar, G.P., Sherman, D., Liang, X.H., Meng, G., Hong, K., Marsters, J.C., Ferrara, N. Nature (2002) [Pubmed]
  27. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Jeltsch, M., Kaipainen, A., Joukov, V., Meng, X., Lakso, M., Rauvala, H., Swartz, M., Fukumura, D., Jain, R.K., Alitalo, K. Science (1997) [Pubmed]
  28. Biopanning and rapid analysis of selective interactive ligands. Giordano, R.J., Cardó-Vila, M., Lahdenranta, J., Pasqualini, R., Arap, W. Nat. Med. (2001) [Pubmed]
  29. HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma. Sgadari, C., Barillari, G., Toschi, E., Carlei, D., Bacigalupo, I., Baccarini, S., Palladino, C., Leone, P., Bugarini, R., Malavasi, L., Cafaro, A., Falchi, M., Valdembri, D., Rezza, G., Bussolino, F., Monini, P., Ensoli, B. Nat. Med. (2002) [Pubmed]
  30. Vascular endothelial growth factor: basic science and clinical progress. Ferrara, N. Endocr. Rev. (2004) [Pubmed]
  31. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. de Vries, C., Escobedo, J.A., Ueno, H., Houck, K., Ferrara, N., Williams, L.T. Science (1992) [Pubmed]
  32. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. Yano, K., Liaw, P.C., Mullington, J.M., Shih, S.C., Okada, H., Bodyak, N., Kang, P.M., Toltl, L., Belikoff, B., Buras, J., Simms, B.T., Mizgerd, J.P., Carmeliet, P., Karumanchi, S.A., Aird, W.C. J. Exp. Med. (2006) [Pubmed]
  33. Downregulation of vascular endothelial growth factor receptors by tumor necrosis factor-alpha in cultured human vascular endothelial cells. Patterson, C., Perrella, M.A., Endege, W.O., Yoshizumi, M., Lee, M.E., Haber, E. J. Clin. Invest. (1996) [Pubmed]
  34. Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. Brogi, E., Schatteman, G., Wu, T., Kim, E.A., Varticovski, L., Keyt, B., Isner, J.M. J. Clin. Invest. (1996) [Pubmed]
  35. Identification of a peptide blocking vascular endothelial growth factor (VEGF)-mediated angiogenesis. Binétruy-Tournaire, R., Demangel, C., Malavaud, B., Vassy, R., Rouyre, S., Kraemer, M., Plouët, J., Derbin, C., Perret, G., Mazié, J.C. EMBO J. (2000) [Pubmed]
  36. Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration. Favier, B., Alam, A., Barron, P., Bonnin, J., Laboudie, P., Fons, P., Mandron, M., Herault, J.P., Neufeld, G., Savi, P., Herbert, J.M., Bono, F. Blood (2006) [Pubmed]
  37. Poly(A)-binding protein-interacting protein 2, a strong regulator of vascular endothelial growth factor mRNA. Onesto, C., Berra, E., Grépin, R., Pagès, G. J. Biol. Chem. (2004) [Pubmed]
  38. HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Gray, M.J., Zhang, J., Ellis, L.M., Semenza, G.L., Evans, D.B., Watowich, S.S., Gallick, G.E. Oncogene (2005) [Pubmed]
  39. VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells. Ohwada, A., Yoshioka, Y., Iwabuchi, K., Nagaoka, I., Dambara, T., Fukuchi, Y. Thorax (2003) [Pubmed]
  40. Nuclear translocation of phosphorylated STAT3 is essential for vascular endothelial growth factor-induced human dermal microvascular endothelial cell migration and tube formation. Yahata, Y., Shirakata, Y., Tokumaru, S., Yamasaki, K., Sayama, K., Hanakawa, Y., Detmar, M., Hashimoto, K. J. Biol. Chem. (2003) [Pubmed]
  41. Vascular endothelial growth factor regulates focal adhesion assembly in human brain microvascular endothelial cells through activation of the focal adhesion kinase and related adhesion focal tyrosine kinase. Avraham, H.K., Lee, T.H., Koh, Y., Kim, T.A., Jiang, S., Sussman, M., Samarel, A.M., Avraham, S. J. Biol. Chem. (2003) [Pubmed]
  42. Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways. Santos, S.C., Dias, S. Blood (2004) [Pubmed]
  43. The adaptor protein Gab1 couples the stimulation of vascular endothelial growth factor receptor-2 to the activation of phosphoinositide 3-kinase. Dance, M., Montagner, A., Yart, A., Masri, B., Audigier, Y., Perret, B., Salles, J.P., Raynal, P. J. Biol. Chem. (2006) [Pubmed]
  44. Expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 (KDR/Flk-1) in ischemic skeletal muscle and its regeneration. Rissanen, T.T., Vajanto, I., Hiltunen, M.O., Rutanen, J., Kettunen, M.I., Niemi, M., Leppänen, P., Turunen, M.P., Markkanen, J.E., Arve, K., Alhava, E., Kauppinen, R.A., Ylä-Herttuala, S. Am. J. Pathol. (2002) [Pubmed]
  45. Calcified rheumatic valve neoangiogenesis is associated with vascular endothelial growth factor expression and osteoblast-like bone formation. Rajamannan, N.M., Nealis, T.B., Subramaniam, M., Pandya, S., Stock, S.R., Ignatiev, C.I., Sebo, T.J., Rosengart, T.K., Edwards, W.D., McCarthy, P.M., Bonow, R.O., Spelsberg, T.C. Circulation (2005) [Pubmed]
  46. Expression of hypoxia-inducible transcription factors in developing human and rat kidneys. Bernhardt, W.M., Schmitt, R., Rosenberger, C., Münchenhagen, P.M., Gröne, H.J., Frei, U., Warnecke, C., Bachmann, S., Wiesener, M.S., Willam, C., Eckardt, K.U. Kidney Int. (2006) [Pubmed]
  47. Pentoxifylline inhibits hypoxia-induced upregulation of tumor cell tissue factor and vascular endothelial growth factor. Amirkhosravi, A., Meyer, T., Warnes, G., Amaya, M., Malik, Z., Biggerstaff, J.P., Siddiqui, F.A., Sherman, P., Francis, J.L. Thromb. Haemost. (1998) [Pubmed]
  48. Co-accumulation of vascular endothelial growth factor with beta-amyloid in the brain of patients with Alzheimer's disease. Yang, S.P., Bae, D.G., Kang, H.J., Gwag, B.J., Gho, Y.S., Chae, C.B. Neurobiol. Aging (2004) [Pubmed]
  49. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Soker, S., Takashima, S., Miao, H.Q., Neufeld, G., Klagsbrun, M. Cell (1998) [Pubmed]
  50. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. Gaudio, E., Barbaro, B., Alvaro, D., Glaser, S., Francis, H., Ueno, Y., Meininger, C.J., Franchitto, A., Onori, P., Marzioni, M., Taffetani, S., Fava, G., Stoica, G., Venter, J., Reichenbach, R., De Morrow, S., Summers, R., Alpini, G. Gastroenterology (2006) [Pubmed]
  51. Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Wang, H., Keiser, J.A. Circ. Res. (1998) [Pubmed]
  52. Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells. Barleon, B., Siemeister, G., Martiny-Baron, G., Weindel, K., Herzog, C., Marmé, D. Cancer Res. (1997) [Pubmed]
  53. CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex. Martin, D., Galisteo, R., Gutkind, J.S. J. Biol. Chem. (2009) [Pubmed]
  54. Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. Yoneda, J., Kuniyasu, H., Crispens, M.A., Price, J.E., Bucana, C.D., Fidler, I.J. J. Natl. Cancer Inst. (1998) [Pubmed]
  55. Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity. Giger, R.J., Urquhart, E.R., Gillespie, S.K., Levengood, D.V., Ginty, D.D., Kolodkin, A.L. Neuron (1998) [Pubmed]
  56. Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling. Shintani, Y., Takashima, S., Asano, Y., Kato, H., Liao, Y., Yamazaki, S., Tsukamoto, O., Seguchi, O., Yamamoto, H., Fukushima, T., Sugahara, K., Kitakaze, M., Hori, M. EMBO J. (2006) [Pubmed]
  57. Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. Fava, R.A., Olsen, N.J., Spencer-Green, G., Yeo, K.T., Yeo, T.K., Berse, B., Jackman, R.W., Senger, D.R., Dvorak, H.F., Brown, L.F. J. Exp. Med. (1994) [Pubmed]
  58. The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells. Sumimoto, H., Imabayashi, F., Iwata, T., Kawakami, Y. J. Exp. Med. (2006) [Pubmed]
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