Systems biology modeling of endothelial cell and macrophage signaling in angiogenesis in human diseases

Zhang, Yu; Zhao, Chen; Popel, Aleksander S.

doi:10.1016/b978-0-12-822546-2.00021-6

The Vasculome 2022

DOI: 10.1016/b978-0-12-822546-2.00021-6

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Systems biology modeling of endothelial cell and macrophage signaling in angiogenesis in human diseases

Yu Zhang,

Chen Zhao,

Aleksander S. Popel

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2023

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Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway

Oliveira

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Popel

2023

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Several signaling pathways are activated during hypoxia to promote angiogenesis, leading to endothelial cell patterning, interaction, and downstream signaling. Understanding the mechanistic signaling differences between normoxia and hypoxia can guide therapies to modulate angiogenesis. We present a novel mechanistic model of interacting endothelial cells, including the main pathways involved in angiogenesis. We calibrate and fit the model parameters based on well-established modeling techniques. Our results indicate that the main pathways involved in the patterning of tip and stalk endothelial cells under hypoxia differ, and the time under hypoxia affects how a reaction affects patterning. Interestingly, the interaction of receptors with Neuropilin1 is also relevant for cell patterning. Our simulations under different oxygen concentrations indicate time- and oxygen-availability-dependent responses for the two cells. Following simulations with various stimuli, our model suggests that factors such as period under hypoxia and oxygen availability must be considered for pattern control. This project provides insights into the signaling and patterning of endothelial cells under hypoxia, contributing to studies in the field.

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Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway

Oliveira

Annex

Popel

2023

Preprint

Self Cite

View full text Add to dashboard Cite

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Systems biology modeling of endothelial cell and macrophage signaling in angiogenesis in human diseases

Cited by 1 publication

References 90 publications

Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway

Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway

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