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 Kato; Mauricio A. Cuello; Fernanda Parborell; Griselda Irusta; Veronica Palma; Miguel L. Allende; Gareth I. Owen

doi:10.1002/jcp.24612

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 journal › Article › peer-review

14 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 language	English (US)
Pages (from-to)	1673-1680
Number of pages	8
Journal	Journal of Cellular Physiology
Volume	229
Issue number	11
DOIs	https://doi.org/10.1002/jcp.24612
State	Published - Nov 2014
Externally published	Yes

ASJC Scopus subject areas

Physiology
Clinical Biochemistry
Cell Biology

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10.1002/jcp.24612

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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

Lange, S, Gonzalez, I, Pinto, MP, Arce, M, Valenzuela, R, Aranda, E, Elliot, M, Alvarez, M, Henriquez, S, Velasquez, EV, Orge, F, Oliva, B, Gonzalez, P, Villalon, M, Cautivo, KM, Kalergis, AM, Pereira, K, Mendoza, C, Saez, C, Kato, S, Cuello, MA, Parborell, F, Irusta, G, Palma, V, Allende, ML & Owen, GI 2014, 'Independent Anti-Angiogenic Capacities of Coagulation Factors X and Xa', Journal of Cellular Physiology, vol. 229, no. 11, pp. 1673-1680. https://doi.org/10.1002/jcp.24612

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

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

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AU - Lange, Soledad

AU - Gonzalez, Ibeth

AU - Pinto, Mauricio P.

AU - Arce, Maximiliano

AU - Valenzuela, Rodrigo

AU - Aranda, Evelyn

AU - Elliot, Matias

AU - Alvarez, Marjorie

AU - Henriquez, Soledad

AU - Velasquez, Ethel V.

AU - Orge, Felipe

AU - Oliva, Barbara

AU - Gonzalez, Pamela

AU - Villalon, Manuel

AU - Cautivo, Kelly M.

AU - Kalergis, Alexis M.

AU - Pereira, Karla

AU - Mendoza, Camila

AU - Saez, Claudia

AU - Kato, Sumie

AU - Cuello, Mauricio A.

AU - Parborell, Fernanda

AU - Irusta, Griselda

AU - Palma, Veronica

AU - Allende, Miguel L.

AU - Owen, Gareth I.

PY - 2014/11

Y1 - 2014/11

N2 - 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.

AB - 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.

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Independent Anti-Angiogenic Capacities of Coagulation Factors X and Xa

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