Display options
Cite
Ahmad S, Hewett PW, Al-Ani B, et al. Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis. Vasc Cell. 2011;3(1):15doi: 10.1186/2045-824X-3-15.
Ahmad, S., Hewett, P. W., Al-Ani, B., Sissaoui, S., Fujisawa, T., Cudmore, M. J., & Ahmed, A. (2011). Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis. Vascular cell, 3(1), 15. https://doi.org/10.1186/2045-824X-3-15
Ahmad, Shakil, et al. "Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis." Vascular cell vol. 3,1 (2011): 15. doi: https://doi.org/10.1186/2045-824X-3-15
Ahmad S, Hewett PW, Al-Ani B, Sissaoui S, Fujisawa T, Cudmore MJ, Ahmed A. Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis. Vasc Cell. 2011 Jul 13;3(1):15. doi: 10.1186/2045-824X-3-15. PMID: 21752276; PMCID: PMC3173355.
Copy Download .nbib Format: NLM
Share it on

Vasc Cell. 2011 Jul 13;3(1):15. doi: 10.1186/2045-824X-3-15.

Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis.

Vascular cell

Shakil Ahmad, Peter W Hewett, Bahjat Al-Ani, Samir Sissaoui, Takeshi Fujisawa, Melissa J Cudmore, Asif Ahmed

Affiliations

  1. University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
  2. Department of Reproductive and Vascular Biology, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, UK.

PMID: 21752276 PMCID: PMC3173355 DOI: 10.1186/2045-824X-3-15

Abstract

BACKGROUND: The negative feedback system is an important physiological regulatory mechanism controlling angiogenesis. Soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), acts as a potent endogenous soluble inhibitor of VEGF- and placenta growth factor (PlGF)-mediated biological function and can also form dominant-negative complexes with competent full-length VEGF receptors.

METHODS AND RESULTS: Systemic overexpression of VEGF-A in mice resulted in significantly elevated circulating sFlt-1. In addition, stimulation of human umbilical vein endothelial cells (HUVEC) with VEGF-A, induced a five-fold increase in sFlt-1 mRNA, a time-dependent significant increase in the release of sFlt-1 into the culture medium and activation of the flt-1 gene promoter. This response was dependent on VEGF receptor-2 (VEGFR-2) and phosphoinositide-3'-kinase signalling. siRNA-mediated knockdown of sFlt-1 in HUVEC stimulated the activation of endothelial nitric oxide synthase, increased basal and VEGF-induced cell migration and enhanced endothelial tube formation on growth factor reduced Matrigel. In contrast, adenoviral overexpression of sFlt-1 suppressed phosphorylation of VEGFR-2 at tyrosine 951 and ERK-1/-2 MAPK and reduced HUVEC proliferation. Preeclampsia is associated with elevated placental and systemic sFlt-1. Phosphorylation of VEGFR-2 tyrosine 951 was greatly reduced in placenta from preeclamptic patients compared to gestationally-matched normal placenta.

CONCLUSION: These results show that endothelial sFlt-1 expression is regulated by VEGF and acts as an autocrine regulator of endothelial cell function.

References

  1. Biochem Biophys Res Commun. 1998 Nov 27;252(3):743-6 - PubMed
  2. Circulation. 2007 Apr 3;115(13):1789-97 - PubMed
  3. Nat Biotechnol. 2004 Mar;22(3):326-30 - PubMed
  4. Biochem Biophys Res Commun. 1996 Sep 13;226(2):324-8 - PubMed
  5. Nature. 1996 Apr 4;380(6573):439-42 - PubMed
  6. Nat Med. 2000 Oct;6(10):1102-3 - PubMed
  7. Nat Med. 2003 Jun;9(6):669-76 - PubMed
  8. Development. 2001 May;128(9):1531-8 - PubMed
  9. J Clin Invest. 2003 Mar;111(5):649-58 - PubMed
  10. Cell. 2007 Aug 24;130(4):691-703 - PubMed
  11. Am J Pathol. 2002 Apr;160(4):1405-23 - PubMed
  12. Am J Pathol. 2001 Sep;159(3):993-1008 - PubMed
  13. J Gene Med. 2002 Jul-Aug;4(4):371-80 - PubMed
  14. N Engl J Med. 2004 Feb 12;350(7):672-83 - PubMed
  15. Development. 2000 Sep;127(18):3941-6 - PubMed
  16. Diabetes. 2003 Dec;52(12):2959-68 - PubMed
  17. Nat Neurosci. 2005 Jan;8(1):85-92 - PubMed
  18. J Biol Chem. 1994 Oct 14;269(41):25646-54 - PubMed
  19. J Biol Chem. 2002 Mar 29;277(13):10760-6 - PubMed
  20. Obstet Gynecol. 2000 Mar;95(3):353-7 - PubMed
  21. J Clin Invest. 1998 Jun 1;101(11):2567-78 - PubMed
  22. Lab Invest. 1997 Jun;76(6):779-91 - PubMed
  23. J Clin Invest. 1997 Dec 15;100(12):3131-9 - PubMed
  24. Circ Res. 2007 Jan 5;100(1):88-95 - PubMed
  25. Surgery. 2002 Nov;132(5):857-65 - PubMed
  26. Mol Cell. 1998 Nov;2(5):549-58 - PubMed
  27. Hypertension. 2010 Mar;55(3):689-97 - PubMed
  28. Circulation. 2000 Aug 22;102(8):898-901 - PubMed
  29. Exp Cell Res. 1998 May 25;241(1):161-70 - PubMed
  30. Circ Res. 2006 Sep 29;99(7):715-22 - PubMed
  31. Nature. 1996 Apr 4;380(6573):435-9 - PubMed
  32. Circ Res. 2002 May 17;90(9):966-73 - PubMed
  33. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5780-5 - PubMed
  34. J Cell Mol Med. 2010 Jun;14(6B):1857-67 - PubMed
  35. Nat Genet. 2001 Jun;28(2):131-8 - PubMed
  36. Nature. 1992 Oct 29;359(6398):843-5 - PubMed
  37. Circ Res. 2004 Oct 29;95(9):884-91 - PubMed

Publication Types

Grant support