title: Independent anti-angiogenic capacities of coagulation factors X and Xa.
abstract: Knockout models have shown that the coagulation system has a role in vascular development and angiogenesis. Herein, we report for the first time that zymogen FX and its active form (FXa) possess anti-angiogenic properties. Both the recombinant FX and FXa inhibit angiogenesis in vitro using endothelial EA.hy926 and human umbilical cord vascular endothelial cells (HUVEC). This effect is dependent on the Gla domain of FX. We demonstrate that FX and FXa use different mechanisms: the use of Rivaroxaban (RX) a specific inhibitor of FXa attenuated its anti-angiogenic properties but did not modify the anti-angiogenic effect of FX. Furthermore, only the anti-angiogenic activity of FXa is PAR-1dependent. Using in vivo models, we show that FX and FXa are anti-angiogenic in the zebrafish intersegmental vasculature (ISV) formation and in the chick embryo chorioallantoic membrane (CAM) assays. Our results provide further evidence for the non-hemostatic functions of FX and FXa and demonstrate for the first time a biological role for the zymogen FX.
authors.affiliation: Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Soledad
authors.initials: S
authors.lastname: Lange
authors.forename: Ibeth
authors.initials: I
authors.lastname: Gonzalez
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Pinto
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Arce
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Valenzuela
authors.forename: Evelyn
authors.initials: E
authors.lastname: Aranda
authors.forename: Matias
authors.initials: M
authors.lastname: Elliot
authors.forename: Marjorie
authors.initials: M
authors.lastname: Alvarez
authors.forename: Soledad
authors.initials: S
authors.lastname: Henriquez
authors.forename: Ethel V
authors.initials: EV
authors.lastname: Velasquez
authors.forename: Felipe
authors.initials: F
authors.lastname: Orge
authors.forename: Barbara
authors.initials: B
authors.lastname: Oliva
authors.forename: Pamela
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Manuel
authors.initials: M
authors.lastname: Villalon
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Cautivo
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.forename: Karla
authors.initials: K
authors.lastname: Pereira
authors.forename: Camila
authors.initials: C
authors.lastname: Mendoza
authors.forename: Claudia
authors.initials: C
authors.lastname: Saez
authors.forename: Sumie
authors.initials: S
authors.lastname: Kato
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Cuello
authors.forename: Fernanda
authors.initials: F
authors.lastname: Parborell
authors.forename: Griselda
authors.initials: G
authors.lastname: Irusta
authors.forename: Veronica
authors.initials: V
authors.lastname: Palma
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Allende
authors.forename: Gareth I
authors.initials: GI
authors.lastname: Owen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D005170:Factor X / Q000494:pharmacology / Q000627:therapeutic use; D015951:Factor Xa / Q000494:pharmacology* / Q000627:therapeutic use; D015801:Helminth Proteins / Q000494:pharmacology / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects; D044463:Receptor, PAR-1 / Q000378:metabolism; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D015801:Helminth Proteins; D044463:Receptor, PAR-1; C400226:anti-coagulant protein C2, Ancylostoma caninum; D005170:Factor X; D015951:Factor Xa