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High mitogenic stimulation arrests angiogenesis

Author

Listed:
  • Samuel Pontes-Quero

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Macarena Fernández-Chacón

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Wen Luo

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Federica Francesca Lunella

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Verónica Casquero-Garcia

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Irene Garcia-Gonzalez

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Ana Hermoso

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Susana F. Rocha

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Mayank Bansal

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Rui Benedito

    (Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC))

Abstract

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.

Suggested Citation

  • Samuel Pontes-Quero & Macarena Fernández-Chacón & Wen Luo & Federica Francesca Lunella & Verónica Casquero-Garcia & Irene Garcia-Gonzalez & Ana Hermoso & Susana F. Rocha & Mayank Bansal & Rui Benedito, 2019. "High mitogenic stimulation arrests angiogenesis," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09875-7
    DOI: 10.1038/s41467-019-09875-7
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    Cited by:

    1. Jeremiah Bernier-Latmani & Cristina Mauri & Rachel Marcone & François Renevey & Stephan Durot & Liqun He & Michael Vanlandewijck & Catherine Maclachlan & Suzel Davanture & Nicola Zamboni & Graham W. K, 2022. "ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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