Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/7542
Título
High mitogenic stimulation arrests angiogenesis
Autor(es)
Pontes-Quero, Samuel CNIC | Fernandez-Chacon, Macarena CNIC | Luo, Wen CNIC | Lunella, Federica Francesca CNIC | Casquero-Garcia, Veronica CNIC | Garcia-Gonzalez, Irene CNIC | Hermoso, Ana CNIC | Rocha, Susana CNIC | Bansal, Mayank CNIC | Benedito, Rui CNIC
Fecha de publicación
2019-05-01
Cita
Nat Commun. 2019; 10(1):2016
Idioma
Inglés
Tipo de documento
journal article
Resumen
Appropriate therapeutic modulation of endothelial proliferation and sprouting is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor concentration, and the resulting mitogenic activity, increases both endothelial proliferation and sprouting. Here, we modulate mitogenic stimuli in different vascular contexts by interfering with the function of the VEGF and Notch signalling pathways at high spatiotemporal resolution in vivo. Contrary to the prevailing view, our results indicate that high mitogenic stimulation induced by VEGF, or Notch inhibition, arrests the proliferation of angiogenic vessels. This is due to the existence of a bell-shaped dose-response to VEGF and MAPK activity that is counteracted by Notch and p21, determining whether endothelial cells sprout, proliferate, or become quiescent. The identified mechanism should be considered to achieve optimal therapeutic modulation of angiogenesis.
Versión en línea
DOI
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