A mechanistic computational model of HGF-VEGF-mediated endothelial cell proliferation and vascular permeability
Rebeca Hannah de Melo Oliveira, Akash Patil, Brian H. Annex, Arvind P. Pathak, Aleksander S. Popel
TL;DR
This paper presents a computational model showing how HGF and VEGF affect blood vessel growth and permeability, revealing how they interact in disease-related processes.
Contribution
A novel data-driven model of HGF and VEGF signaling in endothelial cells that explains their distinct effects on vascular permeability.
Findings
HGF can counteract VEGF-induced endothelial cell permeability in a dose-dependent manner.
RAC1-PAK1 activation via phosphorylation explains differences in permeability between HGF and VEGF.
HGF does not require VEGFR2 activation to influence endothelial cell behavior.
Abstract
Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) are important pro-angiogenic factors in angiogenesis-dependent diseases. While sharing some signaling pathways, their contrasting effect on vascular permeability remains under investigation. To explore how these factors promote angiogenesis, we developed, calibrated, and validated a data-driven mechanistic computational model of HGF and VEGF signaling in endothelial cells (ECs). We proposed that variations in permeability profiles may stem from RAC1-PAK1 activation via site-specific phosphorylation. By introducing permeability and proliferation indices, our simulations indicated a dose-dependent effect of VEGF that hampered the ability of HGF to promote vascular stability. Our simulations indicate that HGF did not require VEGFR2 activation to affect permeability and proliferation. This model has the potential…
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Taxonomy
TopicsAngiogenesis and VEGF in Cancer · Coronary Interventions and Diagnostics · Macrophage Migration Inhibitory Factor