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Related Experiment Video

Updated: Jun 13, 2025

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
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Promoting vascular stability through Src inhibition and Tie2 activation: A model-based analysis.

Yu Zhang1, Christopher D Kontos2, Brian H Annex3

  • 1Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21215, USA.

Iscience
|June 10, 2025
PubMed
Summary

This study models vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-Tie pathways to understand vascular growth and leakage. Chronic Ang1 protects against VEGF-induced leakage, and combined Src inhibition with Tie2 activation may prevent leakage without hindering angiogenesis.

Keywords:
BioinformaticsBiological sciencesNatural sciencesPharmacoinformatics

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Area of Science:

  • Systems biology
  • Molecular biology
  • Vascular biology

Background:

  • Dysregulated angiogenesis causes pathological vascular growth and leakage in diseases like cancer and ocular conditions.
  • Peripheral arterial disease presents challenges due to increased vascular permeability, hindering therapeutic efforts to improve perfusion.
  • Understanding endothelial control of vascular growth and permeability is crucial for developing effective therapies.

Purpose of the Study:

  • To develop a mechanistic systems biology model of the endothelial signaling network involving vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-Tie pathways.
  • To elucidate the mechanisms regulating vascular growth and stability.
  • To identify therapeutic strategies that promote blood vessel growth while maintaining vascular stability.

Main Methods:

  • Developed a mechanistic systems biology model of the VEGF and Ang-Tie signaling pathways.
  • Calibrated and validated the model against experimental data.
  • Utilized the model to predict the effects of specific pathway interventions.

Main Results:

  • Revealed mechanisms by which chronic Ang1 stimulation protects endothelial cells from VEGF-induced hyperpermeability.
  • Demonstrated that the Ang-Tie pathway plays a critical role in maintaining vascular stability.
  • The model predicted that combining Src inhibition with Tie2 activation can inhibit vascular leakage.

Conclusions:

  • Chronic Ang1 stimulation offers protection against VEGF-induced vascular hyperpermeability.
  • Targeting the Ang-Tie pathway is a promising strategy for managing vascular leakage.
  • Combining Src inhibition with Tie2 activation presents a potential therapeutic approach to inhibit vascular leakage without compromising angiogenesis.