title: Impact of Hey2 and COUP-TFII on genes involved in arteriovenous differentiation in primary human arterial and venous endothelial cells.
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.
authors.affiliation: Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus, University of Technology Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Korten
authors.forename: Coy
authors.initials: C
authors.lastname: Brunssen
authors.forename: David M
authors.initials: DM
authors.lastname: Poitz
authors.forename: Sylvia
authors.initials: S
authors.lastname: Großklaus
authors.forename: Melanie
authors.initials: M
authors.lastname: Brux
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schnittler
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Henning
authors.initials: H
authors.lastname: Morawietz
authors.forename: Winfried
authors.initials: W
authors.lastname: Goettsch
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D051837:COUP Transcription Factor II / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D036388:Ephrin-B2 / Q000378:metabolism; D006801:Humans; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014469:Umbilical Arteries / Q000166:cytology / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D051837:COUP Transcription Factor II; D036388:Ephrin-B2; D051880:Receptors, Notch; D012097:Repressor Proteins; D042461:Vascular Endothelial Growth Factor A; C405693:HEY2 protein, human; C095569:NR2F2 protein, human