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Impact of Hey2 and COUP-TFII on genes involved in arteriovenous differentiation in primary human arterial and venous endothelial cells

  • Slobodanka Korten
  • Coy Brunssen
  • David M. Poitz
  • Sylvia Großklaus
  • Melanie Brux
  • Hans-Joachim Schnittler
  • Ruth H. Strasser
  • Stefan R. Bornstein
  • Henning MorawietzEmail author
  • Winfried GoettschEmail author
Original Contribution

Abstract

Arteries and veins show marked differences in their anatomy, physiology and genetic expression pattern. In this study, we analyzed impact of overexpression or downregulation of arterial marker gene Hey2 and venous marker gene COUP-TFII in human venous and arterial endothelial cells on genes involved in arteriovenous differentiation. Lentiviral overexpression of venous marker gene COUP-TFII in arterial endothelial cells led to downregulation of NICD4, arterial marker gene Hey2 and EphrinB2. Downregulation of Hey2 could be mediated by direct binding of COUP-TFII to Hey2 promoter as shown by ChIP, EMSA and promoter analysis. Downregulation of Hey2 by shRNA causes downregulation of EphrinB2 expression. Overexpression of arterial marker Hey2 in venous endothelial cells did not change expression pattern of COUP-TFII. Downregulation of venous marker gene COUP-TFII in venous endothelial cells resulted in upregulation of VEGF-A, Dll4 and EphrinB2 expression. Our data support an important role of Hey2 and COUP-TFII in arteriovenous differentiation of human endothelial cells.

Keywords

Arteriovenous differentiation COUP-TFII Endothelial cells Hey2 Vascular biology 

Notes

Acknowledgments

We thank A. Frenzel, and A. Mieting for excellent technical assistance. This work was supported by grants from Medical Faculty of University of Technology Dresden (MeDDrive program to W.G.), Doktor Robert Pfleger Foundation, Bamberg, Germany (to W.G.), Deutsche Forschungsgemeinschaft (DFG, 1695/4-1, 1695/5-1 to H.M.), Else Kröner-Fresenius-Stiftung (to H.M.) and DFG Center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence (to W.G. and H.M.).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

395_2013_362_MOESM1_ESM.pdf (3.1 mb)
Supplementary material 1 (PDF 3173 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Slobodanka Korten
    • 1
    • 2
  • Coy Brunssen
    • 1
  • David M. Poitz
    • 3
  • Sylvia Großklaus
    • 4
  • Melanie Brux
    • 1
  • Hans-Joachim Schnittler
    • 2
    • 4
    • 5
  • Ruth H. Strasser
    • 2
    • 3
  • Stefan R. Bornstein
    • 2
    • 6
  • Henning Morawietz
    • 1
    • 2
    Email author
  • Winfried Goettsch
    • 1
    • 2
    Email author
  1. 1.Division of Vascular Endothelium and Microcirculation, Department of Medicine IIIUniversity Hospital Carl Gustav Carus, University of Technology DresdenDresdenGermany
  2. 2.Center for Regenerative Therapies Dresden, DFG Research Center, Cluster of ExcellenceDresdenGermany
  3. 3.Department of Internal Medicine and CardiologyDresden Heart CenterDresdenGermany
  4. 4.Department of PhysiologyUniversity of Technology DresdenDresdenGermany
  5. 5.Department of Anatomy and Cell Biology, Institute of AnatomyUniversity of MünsterMünsterGermany
  6. 6.Department of Medicine IIIUniversity Hospital Carl Gustav Carus, University of Technology DresdenDresdenGermany

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