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Gene Review

VEGFA  -  vascular endothelial growth factor A

Ovis aries

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Disease relevance of VEGF

  • Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep [1].
  • We conclude that plasmid-mediated VEGF gene transfer reduces myocardial infarct size by a combination of effects including neovascular proliferation, modification of fibrosis and cardiomyocyte regeneration [1].
  • Notably, ORFV 006/132, 103, 109, 110, and 116 genes (VEGF, homologues of vaccinia virus A26L, A33R, and A34R, and a novel PPV ORF) show an unusual degree of intraspecies variability [2].
  • The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction [3].
  • In many cells, hypoxia stimulates VEGF expression [4].

Psychiatry related information on VEGF


High impact information on VEGF

  • ORFV2-VEGF showed mitogenic activity on bovine aortic and human microvascular endothelial cells and induced vascular permeability [6].
  • These results indicate that VEGF-E is a novel type of endothelial growth factor, utilizing only one of the VEGF receptors, and carrying a potent mitogenic activity without affinity to heparin [7].
  • Recently, a gene encoding a polypeptide with about 25% amino acid identity to mammalian VEGF was identified in the genome of Orf virus (OV), a parapoxvirus that affects sheep and goats and occasionally, humans, to generate lesions with angiogenesis [7].
  • Resting myocardial perfusion (99mTc-sestamibi SPECT) was higher in VEGF-treated group than in empty plasmid group 15 days after myocardial infarction [1].
  • After 15 days infarct area was 11.3+/-1.3% of the left ventricle in the VEGF group and 18.2+/-2.1% in the empty plasmid group (P<0.02) [1].

Chemical compound and disease context of VEGF


Biological context of VEGF


Anatomical context of VEGF

  • Vascular endothelial growth factor (VEGF) has been reported to increase eNOS expression and NO production in endothelial cell cultures [11].
  • The pattern of the rise in NOx in circulating plasma was not directly associated with changes in VEGF regardless of the number of fetuses present [11].
  • However, circulating concentrations of NOx and VEGF appear to, respectively, follow patterns of uterine blood flow and angiogenesis of the uterus [11].
  • CLINICAL RELEVANCE: Exogenous VEGF application for ACL reconstruction can induce an increase in knee laxity and a decrease in the stiffness of the grafted tendon at least temporarily after ACL reconstruction [15].
  • VEGF protein was localized in epithelial cells of the placenta and fetal kidney, and in hepatocytes of the fetal liver [12].

Associations of VEGF with chemical compounds

  • We have previously shown that angiogenic factors from corpora lutea are primarily heparin binding and that one of these factors is similar to vascular endothelial growth factor (VEGF) [16].
  • Similarly, P-UAEC make PGI2 in response to AII, ATP, bFGF, and VEGF, whereas NP-UAEC make PGI2 only in response to ATP and VEGF [17].
  • Thus, P-UAEC make NO in response to AII, ATP, bFGF, EGF, and VEGF, whereas NP-UAEC make NO in response to bFGF, EGF, and VEGF only [17].
  • Therefore, our results indicate that cyclic stretch upregulates VEGF expression via the TGF-beta1-dependent activation of NAD(P)H oxidase and increased generation of ROS [18].
  • Also, in some cases, dexamethasone blocks VEGF expression [4].

Other interactions of VEGF


Analytical, diagnostic and therapeutic context of VEGF

  • In addition, an N-terminal peptide was synthesized from the translated ovine cDNA sequence for VEGF and an antiserum was raised against this peptide for use in western immunoblotting procedures [16].
  • Cloning and sequence analysis of the most abundant form of ovine VEGF cDNA in the placenta confirmed the prediction of a 164-amino acid peptide, with a putative N-terminal signal sequence of 26 amino acids [12].
  • Expression of VEGF and FGF-2 was determined by Northern blot analysis [20].
  • Little is known about the growth factors involved in lung injury and repair, but vascular endothelial growth factor (VEGF) has recently been reported in several animal models of lung injury [4].
  • A significantly lower atrophy score was observed in the groups treated with bFGF (1.4 +/- 0.18, p < 0.05), RGTA (1.59 +/- 0.17, p < 0.05), and VEGF (1.96 +/- 0.14, NS), as compared with the control group (2.48 +/- 0.16) [24].


  1. Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep. Vera Janavel, G., Crottogini, A., Cabeza Meckert, P., Cuniberti, L., Mele, A., Papouchado, M., Fernández, N., Bercovich, A., Criscuolo, M., Melo, C., Laguens, R. Gene Ther. (2006) [Pubmed]
  2. Genomes of the parapoxviruses ORF virus and bovine papular stomatitis virus. Delhon, G., Tulman, E.R., Afonso, C.L., Lu, Z., de la Concha-Bermejillo, A., Lehmkuhl, H.D., Piccone, M.E., Kutish, G.F., Rock, D.L. J. Virol. (2004) [Pubmed]
  3. The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction. Regnault, T.R., de Vrijer, B., Galan, H.L., Davidsen, M.L., Trembler, K.A., Battaglia, F.C., Wilkening, R.B., Anthony, R.V. J. Physiol. (Lond.) (2003) [Pubmed]
  4. Vascular endothelial growth factor is expressed in ovine pulmonary vascular smooth muscle cells in vitro and regulated by hypoxia and dexamethasone. Klekamp, J.G., Jarzecka, K., Hoover, R.L., Summar, M.L., Redmond, N., Perkett, E.A. Pediatr. Res. (1997) [Pubmed]
  5. Angiogenic growth factors and/or cellular therapy for myocardial regeneration: a comparative study. Chachques, J.C., Duarte, F., Cattadori, B., Shafy, A., Lila, N., Chatellier, G., Fabiani, J.N., Carpentier, A.F. J. Thorac. Cardiovasc. Surg. (2004) [Pubmed]
  6. Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1. Wise, L.M., Veikkola, T., Mercer, A.A., Savory, L.J., Fleming, S.B., Caesar, C., Vitali, A., Makinen, T., Alitalo, K., Stacker, S.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. Ogawa, S., Oku, A., Sawano, A., Yamaguchi, S., Yazaki, Y., Shibuya, M. J. Biol. Chem. (1998) [Pubmed]
  8. VEGF regulates remodeling during permanent anatomic closure of the ductus arteriosus. Clyman, R.I., Seidner, S.R., Kajino, H., Roman, C., Koch, C.J., Ferrara, N., Waleh, N., Mauray, F., Chen, Y.Q., Perkett, E.A., Quinn, T. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2002) [Pubmed]
  9. Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus. Levin, M., McCurnin, D., Seidner, S.R., Yoder, B., Waleh, N., Goldbarg, S., Roman, C., Liu, B.M., Borén, J., Clyman, R.I. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  10. Effects of chronic heparin administration on coronary vascular adaptation to hypertension and ventricular hypertrophy in sheep. Flanagan, M.F., Aoyagi, T., Arnold, L.W., Maute, C., Fujii, A.M., Currier, J., Bergau, D., Warren, H.B., Rakusan, K. Circulation (1999) [Pubmed]
  11. Circulating levels of nitric oxide and vascular endothelial growth factor throughout ovine pregnancy. Vonnahme, K.A., Wilson, M.E., Li, Y., Rupnow, H.L., Phernetton, T.M., Ford, S.P., Magness, R.R. J. Physiol. (Lond.) (2005) [Pubmed]
  12. Ovine vascular endothelial growth factor: nucleotide sequence and expression in fetal tissues. Cheung, C.Y., Brace, R.A. Growth Factors (1998) [Pubmed]
  13. Activation of the mitogen-activated protein kinase cascade is necessary but not sufficient for basic fibroblast growth factor- and epidermal growth factor-stimulated expression of endothelial nitric oxide synthase in ovine fetoplacental artery endothelial cells. Zheng, J., Bird, I.M., Melsaether, A.N., Magness, R.R. Endocrinology (1999) [Pubmed]
  14. Evidence for a role of capillary pericytes in vascular growth of the developing ovine corpus luteum. Redmer, D.A., Doraiswamy, V., Bortnem, B.J., Fisher, K., Jablonka-Shariff, A., Grazul-Bilska, A.T., Reynolds, L.P. Biol. Reprod. (2001) [Pubmed]
  15. Effects of local administration of vascular endothelial growth factor on mechanical characteristics of the semitendinosus tendon graft after anterior cruciate ligament reconstruction in sheep. Yoshikawa, T., Tohyama, H., Katsura, T., Kondo, E., Kotani, Y., Matsumoto, H., Toyama, Y., Yasuda, K. The American journal of sports medicine (2006) [Pubmed]
  16. Characterization and expression of vascular endothelial growth factor (VEGF) in the ovine corpus luteum. Redmer, D.A., Dai, Y., Li, J., Charnock-Jones, D.S., Smith, S.K., Reynolds, L.P., Moor, R.M. J. Reprod. Fertil. (1996) [Pubmed]
  17. Pregnancy-dependent changes in cell signaling underlie changes in differential control of vasodilator production in uterine artery endothelial cells. Bird, I.M., Sullivan, J.A., Di, T., Cale, J.M., Zhang, L., Zheng, J., Magness, R.R. Endocrinology (2000) [Pubmed]
  18. Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-beta1 and reactive oxygen species: a requirement for NAD(P)H oxidase. Mata-Greenwood, E., Grobe, A., Kumar, S., Noskina, Y., Black, S.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  19. The effects of acute nutrient restriction in the mid-gestational ewe on maternal and fetal nutrient status, the expression of placental growth factors and fetal growth. McMullen, S., Osgerby, J.C., Milne, J.S., Wallace, J.M., Wathes, D.C. Placenta (2005) [Pubmed]
  20. Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. Quinn, T.P., Schlueter, M., Soifer, S.J., Gutierrez, J.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  21. The angiogenic peptide vascular endothelial growth factor (VEGF) is expressed during the remodeling of free tendon grafts in sheep. Petersen, W., Unterhauser, F., Pufe, T., Zantop, T., Südkamp, N.P., Weiler, A. Archives of orthopaedic and trauma surgery. (2003) [Pubmed]
  22. Intrauterine hypertension decreases lung VEGF expression and VEGF inhibition causes pulmonary hypertension in the ovine fetus. Grover, T.R., Parker, T.A., Zenge, J.P., Markham, N.E., Kinsella, J.P., Abman, S.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  23. Pattern and localisation of expression of vascular endothelial growth factor and its receptor flt-1 in the ovine pituitary gland: expression is independent of hypothalamic control. Jabbour, H.N., Boddy, S.C., Lincoln, G.A. Mol. Cell. Endocrinol. (1997) [Pubmed]
  24. Growth factors improve latissimus dorsi muscle vascularization and trophicity after cardiomyoplasty. Zakine, G., Martinod, E., Fornes, P., Sapoval, M., Barritault, D., Carpentier, A.F., Chachques, J.C. Ann. Thorac. Surg. (2003) [Pubmed]
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