title: Regulation of Angiogenic Functions by Angiopoietins through Calcium-Dependent Signaling Pathways.
abstract: Angiopoietins are vascular factors essential for blood vessel assembly and correct organization and maturation. This study describes a novel calcium-dependent machinery activated through Angiopoietin-1/2-Tie receptor system in HUVECs monolayer. Both cytokines were found to elicit intracellular calcium mobilization. Targeting intracellular Ca(2+) signaling, antagonizing IP3 with 2-APB or cADPR with 8Br-cADPR, was found to modulate in vitro angiogenic responses to Angiopoietins in a specific way. 2-APB and 8Br-cADPR impaired the phosphorylation of AKT and FAK induced by Ang-1 and Ang-2. On the other hand, phosphorylation of ERK1/2 and p38, as well as cell proliferation, was not affected by either inhibitor. The ability of ECs to migrate following Angs stimulation, evaluated by "scratch assay," was reduced by either 2-APB or 8Br-cADPR following Ang-2 stimulation and only slightly affected by 2-APB in cells stimulated with Ang-1. These results identify a novel calcium-dependent machinery involved in the complex interplay regulating angiogenic processes showing that IP3- and cADPR-induced Ca(2+) release specifically regulates distinct Angs-mediated angiogenic steps.
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Pafumi
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Favia
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy ; Institute of Vegetative Anatomy, Charité Universitätsmedizin, Neuromuscular Group, 10115 Berlin, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Gambara
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Papacci
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Ziparo
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Fioretta
authors.initials: F
authors.lastname: Palombi
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Filippini
mesh_terms: D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D036563:Cyclic ADP-Ribose / Q000096:biosynthesis / Q000235:genetics*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000235:genetics*; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D042682:Angiopoietins; D000804:Angiotensin II; D036563:Cyclic ADP-Ribose; D042787:Receptor, TIE-2; D002118:Calcium