2026-06-14T03:32:21Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/75422024-09-27T08:19:48Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Pontes-Quero, Samuel author Fernandez-Chacon, Macarena author Luo, Wen author Lunella, Federica Francesca author Casquero-Garcia, Veronica author Garcia-Gonzalez, Irene author Hermoso, Ana author Rocha, Susana author Bansal, Mayank author Benedito, Rui author 2019-05-01 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. Nat Commun. 2019; 10(1):2016 10.1038/s41467-019-09875-7 2041-1723 2041-1723 Nature communications 31043605 http://hdl.handle.net/20.500.12105/7542 High mitogenic stimulation arrests angiogenesis