title: Urotensin-II-stimulated expression of pro-angiogenic factors in human vascular endothelial cells.
abstract: Urotensin-II (U-II) is an endogenous peptide recently characterized as a "nonclassic" pro-angiogenic cytokine. In fact, human vascular endothelial cells express the U-II receptor and exhibit a strong in vitro angiogenic response to the peptide, which was specifically triggered by the binding of U-II to its receptor and involved the activation of ERK1/2 and PI3K/Akt signaling pathways. Moreover, available studies, designed to investigate the pro-angiogenic effect quite shortly following U-II stimulation, suggested that the angiogenic action of the peptide was direct and not associated with an increased expression of vascular endothelial growth factor (VEGF) and/or its receptors. In the present study, the expression of three pro-angiogenic factors, namely VEGF, endothelin-1, and adrenomedullin, was studied in human umbilical vein endothelial cells (HUVEC) for longer times of U-II stimulation. RT-PCR and Western blot indicated that in HUVEC, exposed for at least 24h to U-II, the expression of the three angiogenic molecules was significantly increased at both mRNA and protein level, opening the possibility that U-II, not only could exert a direct stimulation of an angiogenic phenotype in endothelial cells quite shortly following exposure to the peptide, but could also further enhance the process indirectly by inducing in the cells a delayed production of other pro-angiogenic factors. Interestingly, a preliminary analysis of the time course of the in vitro capillary-like pattern formation was consistent with this view, suggesting a two phase temporal dynamics of the process.
authors.affiliation: Department of Human Anatomy and Physiology (Section of Anatomy), University of Padova Medical School, Padova, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Albertin
authors.forename: Diego
authors.initials: D
authors.lastname: Guidolin
authors.forename: Elisa
authors.initials: E
authors.lastname: Sorato
authors.forename: Barbara
authors.initials: B
authors.lastname: Oselladore
authors.forename: Cinzia
authors.initials: C
authors.lastname: Tortorella
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D060888:Real-Time Polymerase Chain Reaction; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D014579:Urotensins / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D014579:Urotensins; D042461:Vascular Endothelial Growth Factor A; C029677:urotensin II; D040262:Receptors, Vascular Endothelial Growth Factor