Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling
OBJECTIVE: We aim to quantitatively characterize the crosstalk between VEGF‐ and FGF‐mediated angiogenic signaling and endothelial sprouting, to gain mechanistic insights and identify novel therapeutic strategies. METHODS: We constructed an experimentally validated hybrid agent‐based mathematical mo...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285777/ https://www.ncbi.nlm.nih.gov/pubmed/34890488 http://dx.doi.org/10.1111/micc.12744 |
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author | Song, Min Finley, Stacey D. |
author_facet | Song, Min Finley, Stacey D. |
author_sort | Song, Min |
collection | PubMed |
description | OBJECTIVE: We aim to quantitatively characterize the crosstalk between VEGF‐ and FGF‐mediated angiogenic signaling and endothelial sprouting, to gain mechanistic insights and identify novel therapeutic strategies. METHODS: We constructed an experimentally validated hybrid agent‐based mathematical model that characterizes endothelial sprouting driven by FGF‐ and VEGF‐mediated signaling. We predicted the total sprout length, number of sprouts, and average length by the mono‐ and co‐stimulation of FGF and VEGF. RESULTS: The experimentally fitted and validated model predicts that FGF induces stronger angiogenic responses in the long‐term compared with VEGF stimulation. Also, FGF plays a dominant role in the combination effects in endothelial sprouting. Moreover, the model suggests that ERK and Akt pathways and cellular responses contribute differently to the sprouting process. Last, the model predicts that the strategies to modulate endothelial sprouting are context‐dependent, and our model can identify potential effective pro‐ and anti‐angiogenic targets under different conditions and study their efficacy. CONCLUSIONS: The model provides detailed mechanistic insight into VEGF and FGF interactions in sprouting angiogenesis. More broadly, this model can be utilized to identify targets that influence angiogenic signaling leading to endothelial sprouting and to study the effects of pro‐ and anti‐angiogenic therapies. |
format | Online Article Text |
id | pubmed-9285777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92857772022-07-18 Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling Song, Min Finley, Stacey D. Microcirculation Original Articles OBJECTIVE: We aim to quantitatively characterize the crosstalk between VEGF‐ and FGF‐mediated angiogenic signaling and endothelial sprouting, to gain mechanistic insights and identify novel therapeutic strategies. METHODS: We constructed an experimentally validated hybrid agent‐based mathematical model that characterizes endothelial sprouting driven by FGF‐ and VEGF‐mediated signaling. We predicted the total sprout length, number of sprouts, and average length by the mono‐ and co‐stimulation of FGF and VEGF. RESULTS: The experimentally fitted and validated model predicts that FGF induces stronger angiogenic responses in the long‐term compared with VEGF stimulation. Also, FGF plays a dominant role in the combination effects in endothelial sprouting. Moreover, the model suggests that ERK and Akt pathways and cellular responses contribute differently to the sprouting process. Last, the model predicts that the strategies to modulate endothelial sprouting are context‐dependent, and our model can identify potential effective pro‐ and anti‐angiogenic targets under different conditions and study their efficacy. CONCLUSIONS: The model provides detailed mechanistic insight into VEGF and FGF interactions in sprouting angiogenesis. More broadly, this model can be utilized to identify targets that influence angiogenic signaling leading to endothelial sprouting and to study the effects of pro‐ and anti‐angiogenic therapies. John Wiley and Sons Inc. 2021-12-28 2022-02 /pmc/articles/PMC9285777/ /pubmed/34890488 http://dx.doi.org/10.1111/micc.12744 Text en © 2021 The Authors. Microcirculation published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Song, Min Finley, Stacey D. Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling |
title | Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling |
title_full | Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling |
title_fullStr | Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling |
title_full_unstemmed | Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling |
title_short | Mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling |
title_sort | mechanistic characterization of endothelial sprouting mediated by pro‐angiogenic signaling |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285777/ https://www.ncbi.nlm.nih.gov/pubmed/34890488 http://dx.doi.org/10.1111/micc.12744 |
work_keys_str_mv | AT songmin mechanisticcharacterizationofendothelialsproutingmediatedbyproangiogenicsignaling AT finleystaceyd mechanisticcharacterizationofendothelialsproutingmediatedbyproangiogenicsignaling |