title: Molecular characterization of EG-VEGF-mediated angiogenesis: differential effects on microvascular and macrovascular endothelial cells.
abstract: Endocrine gland derived vascular endothelial growth factor (EG-VEGF) also called prokineticin (PK1), has been identified and linked to several biological processes including angiogenesis. EG-VEGF is abundantly expressed in the highest vascularized organ, the human placenta. Here we characterized its angiogenic effect using different experimental procedures. Immunohistochemistry was used to localize EG-VEGF receptors (PROKR1 and PROKR2) in placental and umbilical cord tissue. Primary microvascular placental endothelial cell (HPEC) and umbilical vein-derived macrovascular EC (HUVEC) were used to assess its effects on proliferation, migration, cell survival, pseudovascular organization, spheroid sprouting, permeability and paracellular transport. siRNA and neutralizing antibody strategies were used to differentiate PROKR1- from PROKR2-mediated effects. Our results show that 1) HPEC and HUVEC express both types of receptors 2) EG-VEGF stimulates HPEC's proliferation, migration and survival, but increases only survival in HUVECs. and 3) EG-VEGF was more potent than VEGF in stimulating HPEC sprout formation, pseudovascular organization, and it significantly increases HPEC permeability and paracellular transport. More importantly, we demonstrated that PROKR1 mediates EG-VEGF angiogenic effects, whereas PROKR2 mediates cellular permeability. Altogether, these data characterized angiogenic processes mediated by EG-VEGF, depicted a new angiogenic factor in the placenta, and suggest a novel view of the regulation of angiogenesis in placental pathologies.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 878, Grenoble, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouillet
authors.forename: Pascale
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benharouga
authors.forename: Aude
authors.initials: A
authors.lastname: Salomon
authors.forename: Jean-Patrick
authors.initials: JP
authors.lastname: Schaal
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Feige
authors.forename: Nadia
authors.initials: N
authors.lastname: Alfaidy
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002463:Cell Membrane Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010920:Placenta / Q000098:blood supply / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014470:Umbilical Cord / Q000098:blood supply / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000494:pharmacology*
chemical_list: C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042461:Vascular Endothelial Growth Factor A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D020928:Mitogen-Activated Protein Kinases