April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
The CYP4A-20-HETE System in Regulation of Cord Blood Derived Endothelial Progenitor Cells
Author Affiliations & Notes
  • J. Sheng
    Eye Care Services,
    Henry Ford Health System, Detroit, Michigan
  • A. M. Guo
    Women's health Services,
    Henry Ford Health System, Detroit, Michigan
  • A.-A. Syed
    Radiology,
    Henry Ford Health System, Detroit, Michigan
  • B. Janic
    Radiology,
    Henry Ford Health System, Detroit, Michigan
  • P. A. Edwards
    Dept of Ophthal and Eye Care Services,
    Henry Ford Health System, Detroit, Michigan
  • A. G. Scicli
    Eye Care Services,
    Henry Ford Health System, Detroit, Michigan
  • Footnotes
    Commercial Relationships  J. Sheng, None; A.M. Guo, None; A.-A. Syed, None; B. Janic, None; P.A. Edwards, None; A.G. Scicli, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2665. doi:https://doi.org/
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      J. Sheng, A. M. Guo, A.-A. Syed, B. Janic, P. A. Edwards, A. G. Scicli; The CYP4A-20-HETE System in Regulation of Cord Blood Derived Endothelial Progenitor Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2665. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Introduction: : 20-hydroxyeicosatetraenoic acid (20-HETE) is an arachidonic acid metabolite produced by Cytochrome P450 (CYP) ω-hydroxylases. We have reported that 20-HETE is angiogenic and 20-HETE synthase inhibitors decrease and even suppress angiogenesis induced by growth factors. In human, the more critical 20-HETE synthases are CYP4A11/4A22 and CYP4F2. Endothelial progenitor cells (EPC) are an important component of neovascularization processes.

Purpose: : We studied whether the CYP4A-20-HETE system can contribute to the regulation of EPC.

Methods: : Progenitor cells were isolated from human umbilical cord blood and were identified by AC133 and CD34 expression.

Results: : We found that these EPC contained both immuno-reactive CYP4A11 and CYP4F2. RT-PCR showed that the mRNA’s coding for these enzymes were also present. When EPC were incubated with arachidonic acid, they formed and secreted 20-HETE. These results indicate that EPC contain an active CYP-20-HETE system. Furthermore, stimulation with 20-HETE increased EPC proliferation and migration indicating that 20-HETE can influence EPC functions. When matrigel plugs containing 20-HETE were injected sc in nude mice, a marked angiogenic response was observed. To study whether the injection of labeled EPC iv results in their accumulation into the 20-HETE-containing plug, we used iron-labeled EPC and determined the presence of the labeled EPC in the plug by MRI and immunohistochemistry. These labeled EPC accumulate into the site of 20-HETE induced neovascularization, which suggests that 20-HETE may induce the homing of EPC. Tube formation by EC seed in matrigel is an in vitro model of angiogenesis. We found that co-culture of EC and EPC results in the tube formation and this effect was inhibited by inhibitors of cytochrome P450 4A/F ω-hydroxylases and by a 20-HETE competitive antagonist. This suggests that 20-HETE is involved in EPC-induced tube formation.

Conclusions: : The results suggest that the CYP4A-20-HETE system is involved in regulation of EPC functions associated to angiogenesis.

Keywords: eicosanoids • neovascularization • enzymes/enzyme inhibitors 
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