2026-06-14T03:29:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/75422024-09-27T08:19:48Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación ProCNIC
funder
Fundación La Caixa
2019-05-07T07:55:10Z
2019-05-07T07:55:10Z
2019-05-01
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
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.
eng
High mitogenic stimulation arrests angiogenesis
journal article
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HighMitogenicStimulationArrests_2019.pdf.txt
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HighMitogenicStimulationArrests_2019_MOESM1_ESM.pdf.txt
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