Independent Anti-Angiogenic Capacities of Coagulation Factors X and Xa

Soledad Lange, Ibeth Gonzalez, Mauricio P. Pinto, Maximiliano Arce, Rodrigo Valenzuela, Evelyn Aranda, Matias Elliot, Marjorie Alvarez, Soledad Henriquez, Ethel V. Velasquez, Felipe Orge, Barbara Oliva, Pamela Gonzalez, Manuel Villalon, Kelly M. Cautivo, Alexis M. Kalergis, Karla Pereira, Camila Mendoza, Claudia Saez, Sumie KatoMauricio A. Cuello, Fernanda Parborell, Griselda Irusta, Veronica Palma, Miguel L. Allende, Gareth I. Owen

Research output: Contribution to journalArticle

8 Scopus citations

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. J. Cell. Physiol. 229: 1673-1680, 2014.

Original languageEnglish (US)
Pages (from-to)1673-1680
Number of pages8
JournalJournal of Cellular Physiology
Volume229
Issue number11
DOIs
StatePublished - Nov 2014

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ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Lange, S., Gonzalez, I., Pinto, M. P., Arce, M., Valenzuela, R., Aranda, E., Elliot, M., Alvarez, M., Henriquez, S., Velasquez, E. V., Orge, F., Oliva, B., Gonzalez, P., Villalon, M., Cautivo, K. M., Kalergis, A. M., Pereira, K., Mendoza, C., Saez, C., ... Owen, G. I. (2014). Independent Anti-Angiogenic Capacities of Coagulation Factors X and Xa. Journal of Cellular Physiology, 229(11), 1673-1680. https://doi.org/10.1002/jcp.24612