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Gene Review

VEGFA  -  vascular endothelial growth factor A

Macaca mulatta

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Disease relevance of VEGF


High impact information on VEGF


Biological context of VEGF

  • In addition, analysis of gene expression during hemangioblast development demonstrates that TPO is capable of increasing the mRNA expression of the VEGF receptor (VEGFR) and its own receptor (c-mpl) [8].
  • In this report, we used in situ hybridization to evaluate VEGF, VEGF receptor type 1 and VEGF receptor type 2 mRNA expression during hormonally regulated menstrual cycles in ovariectomized macaques [9].
  • After documenting two normal ovulatory cycles, female rhesus monkeys (n = 7) received iv injections of anti-VEGF antibodies (0.5 mg) twice on successive days in the late follicular phase [10].
  • The data suggest that acute exposure to a VEGF antagonist can impair ovulation, and the subsequent development and functional capacity of the primate corpus luteum [11].
  • VEGF mRNA levels increased (P: < 0.05) from early to mid-luteal phase and declined in the late luteal phase and at menstruation [12].

Anatomical context of VEGF


Associations of VEGF with chemical compounds

  • Culture medium was assayed for VEGF and progesterone [13].
  • Also, higher levels of LIF and TGF beta together with lower levels of VEGF in the vascular compartment in mifepristone-exposed endometrium suggest that endometrial vascular physiology is a target of this anti-progestin during the peri-implantation stage [15].
  • The application of MAb to VEGF during the periimplantation period, on the other hand, led to significant (p<.04) prevention of pregnancy without influencing steroid hormone levels in the circulation [16].
  • VEGF concentrations also declined (P < 0.05) in control, CoCl2, and CoCl2 + LH groups in 0% O2, although CoCl2 modestly increased (75% above control; P < 0.05) VEGF levels in 20% and 5% O2 [17].
  • RESULTS: All 5 bioactive VEGF-injected eyes developed neovascularization with dilated and tortuous iris vessels that leaked fluorescein [18].

Regulatory relationships of VEGF

  • Studies were designed to evaluate the effects of an in vivo gonadotropin surge on VEGF production by macaque granulosa cells (study 1) and to test the hypothesis that gonadotropins act directly on granulosa cells to regulate VEGF production (study 2) [13].
  • In the absence of serum, VEGF stimulated proliferation of UEA-1 (+) cells plated on fibronectin but not collagen I, whereas in the presence of 10% fetal calf serum, both matrices supported VEGF-induced mitogenesis [19].

Other interactions of VEGF

  • Mifepristone used in EC in the present study resulted in general loss of functional integrity of epithelial compartment characterized by loss of secretory maturation, increased apoptosis and higher degree of degeneration along with decreased expression of VEGF, LIF, PP14 and ER, while PR level increased as compared to control samples [20].
  • COX-2 and VEGF RNA, protein, and PGE(2) levels were quantified by RT-PCR, Western analysis, and enzyme immunoassay, respectively [14].
  • Our data lend support to the hypothesis that VEGF is essential for pregnancy establishment and that trophoblast-derived VEGF, acting via its specific receptors Flt-1 and KDR, is necessary for blastocyst implantation [16].
  • LH treatment increased media progesterone (p < 0.05) and vascular endothelial growth factor (VEGF; p < 0.05) levels as well as stimulating expression of mRNAs for MMP-1 (p = 0.05), MMP-9 (p < 0.05), and TIMP-1 (p < 0.05), similar to the effects of an ovulatory dose of gonadotropin in vivo [21].

Analytical, diagnostic and therapeutic context of VEGF


  1. Nonhuman primate models for diabetic ocular neovascularization using AAV2-mediated overexpression of vascular endothelial growth factor. Lebherz, C., Maguire, A.M., Auricchio, A., Tang, W., Aleman, T.S., Wei, Z., Grant, R., Cideciyan, A.V., Jacobson, S.G., Wilson, J.M., Bennett, J. Diabetes (2005) [Pubmed]
  2. Constitutive expression of VEGF, VEGFR-1, and VEGFR-2 in normal eyes. Kim, I., Ryan, A.M., Rohan, R., Amano, S., Agular, S., Miller, J.W., Adamis, A.P. Invest. Ophthalmol. Vis. Sci. (1999) [Pubmed]
  3. Hypoxia activates matrix metalloproteinase expression and the VEGF system in monkey choroid-retinal endothelial cells: Involvement of cytosolic phospholipase A2 activity. Ottino, P., Finley, J., Rojo, E., Ottlecz, A., Lambrou, G.N., Bazan, H.E., Bazan, N.G. Mol. Vis. (2004) [Pubmed]
  4. Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia. Kalaria, R.N., Cohen, D.L., Premkumar, D.R., Nag, S., LaManna, J.C., Lust, W.D. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  5. Vascular remodeling is airway generation-specific in a primate model of chronic asthma. Avdalovic, M.V., Putney, L.F., Schelegle, E.S., Miller, L., Usachenko, J.L., Tyler, N.K., Plopper, C.G., Gershwin, L.J., Hyde, D.M. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  6. Cellular expression and hormonal regulation of neuropilin-1 and -2 messenger ribonucleic Acid in the human and rhesus macaque endometrium. Germeyer, A., Hamilton, A.E., Laughlin, L.S., Lasley, B.L., Brenner, R.M., Giudice, L.C., Nayak, N.R. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  7. Vascular endothelial growth factor Trap suppresses ovarian function at all stages of the luteal phase in the macaque. Fraser, H.M., Wilson, H., Morris, K.D., Swanston, I., Wiegand, S.J. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  8. Thrombopoietin regulates differentiation of rhesus monkey embryonic stem cells to hematopoietic cells. Wang, Z., Skokowa, J., Pramono, A., Ballmaier, M., Welte, K. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  9. Vascular proliferation and vascular endothelial growth factor expression in the rhesus macaque endometrium. Nayak, N.R., Brenner, R.M. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  10. Short-term administration of antivascular endothelial growth factor antibody in the late follicular phase delays follicular development in the rhesus monkey. Zimmermann, R.C., Xiao, E., Husami, N., Sauer, M.V., Lobo, R., Kitajewski, J., Ferin, M. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  11. Injection of soluble vascular endothelial growth factor receptor 1 into the preovulatory follicle disrupts ovulation and subsequent luteal function in rhesus monkeys. Hazzard, T.M., Xu, F., Stouffer, R.L. Biol. Reprod. (2002) [Pubmed]
  12. Changes in expression of vascular endothelial growth factor and angiopoietin-1 and -2 in the macaque corpus luteum during the menstrual cycle. Hazzard, T.M., Christenson, L.K., Stouffer, R.L. Mol. Hum. Reprod. (2000) [Pubmed]
  13. Follicle-stimulating hormone and luteinizing hormone/chorionic gonadotropin stimulation of vascular endothelial growth factor production by macaque granulosa cells from pre- and periovulatory follicles. Christenson, L.K., Stouffer, R.L. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  14. Coordinate activation of HIF-1 and NF-kappaB DNA binding and COX-2 and VEGF expression in retinal cells by hypoxia. Lukiw, W.J., Ottlecz, A., Lambrou, G., Grueninger, M., Finley, J., Thompson, H.W., Bazan, N.G. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  15. Effect of early luteal phase administration of mifepristone (RU486) on leukaemia inhibitory factor, transforming growth factor beta and vascular endothelial growth factor in the implantation stage endometrium of the rhesus monkey. Ghosh, D., Kumar, P.G., Sengupta, J. J. Endocrinol. (1998) [Pubmed]
  16. Target-oriented anti-implantation approaches for pregnancy interception: experiences in the rhesus monkey model. Ghosh, D., Sengupta, J. Contraception. (2005) [Pubmed]
  17. Insulin-like growth factors-1 and -2, but not hypoxia, synergize with gonadotropin hormone to promote vascular endothelial growth factor-A secretion by monkey granulosa cells from preovulatory follicles. Martinez-Chequer, J.C., Stouffer, R.L., Hazzard, T.M., Patton, P.E., Molskness, T.A. Biol. Reprod. (2003) [Pubmed]
  18. Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate. Tolentino, M.J., Miller, J.W., Gragoudas, E.S., Chatzistefanou, K., Ferrara, N., Adamis, A.P. Arch. Ophthalmol. (1996) [Pubmed]
  19. Isolation and culture of microvascular endothelial cells from the primate corpus luteum. Christenson, L.K., Stouffer, R.L. Biol. Reprod. (1996) [Pubmed]
  20. A multiparametric study of the action of mifepristone used in emergency contraception using the Rhesus monkey as a primate model. Sengupta, J., Dhawan, L., Lalitkumar, P.G., Ghosh, D. Contraception. (2003) [Pubmed]
  21. Luteinizing hormone acts directly at granulosa cells to stimulate periovulatory processes: modulation of luteinizing hormone effects by prostaglandins. Duffy, D.M., Stouffer, R.L. Endocrine (2003) [Pubmed]
  22. Vascular endothelial growth factor (VEGF) production by the monkey corpus luteum during the menstrual cycle: isoform-selective messenger RNA expression in vivo and hypoxia-regulated protein secretion in vitro. Tesone, M., Stouffer, R.L., Borman, S.M., Hennebold, J.D., Molskness, T.A. Biol. Reprod. (2005) [Pubmed]
  23. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Adamis, A.P., Shima, D.T., Tolentino, M.J., Gragoudas, E.S., Ferrara, N., Folkman, J., D'Amore, P.A., Miller, J.W. Arch. Ophthalmol. (1996) [Pubmed]
  24. VEGF, bFGF and their receptors at the fetal-maternal interface of the rhesus monkey. Wei, P., Yu, F.Q., Chen, X.L., Tao, S.X., Han, C.S., Liu, Y.X. Placenta (2004) [Pubmed]
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