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Updated: May 29, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis
Corban G Rivera1, Sofie Mellberg, Lena Claesson-Welsh
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America. cgrivera@jhu.edu
Abstract:
Angiogenesis is important for many physiological processes, diseases, and also regenerative medicine. Therapies that inhibit the vascular endothelial growth factor (VEGF) pathway have been used in the clinic for cancer and macular degeneration. In cancer applications, these treatments suffer from a "tumor escape phenomenon" where alternative pathways are upregulated and angiogenesis continues. The redundancy of angiogenesis regulation indicates the need for additional studies and new drug targets. We aimed to (i) identify novel and missing angiogenesis annotations and (ii) verify their significance to angiogenesis. To achieve these goals, we integrated the human interactome with known angiogenesis-annotated proteins to identify a set of 202 angiogenesis-associated proteins. Across endothelial cell lines, we found that a significant fraction of these proteins had highly perturbed gene expression during angiogenesis. After treatment with VEGF-A, we found increasing expression of HIF-1α, APP, HIV-1 tat interactive protein 2, and MEF2C, while endoglin, liprin β1 and HIF-2α had decreasing expression across three endothelial cell lines. The analysis showed differential regulation of HIF-1α and HIF-2α. The data also provided additional evidence for the role of endothelial cells in Alzheimer's disease.
Insights
Researchers identified 202 new proteins linked to angiogenesis, the process of new blood vessel formation. This discovery offers potential new drug targets to combat diseases like cancer and macular degeneration.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Angiogenesis is crucial for physiological processes, diseases, and regenerative medicine.
- Vascular endothelial growth factor (VEGF) pathway inhibitors are used for cancer and macular degeneration but face challenges like tumor escape.
- The complex regulation of angiogenesis necessitates further research into novel pathways and drug targets.
Purpose of the Study:
- To identify novel and missing angiogenesis annotations.
- To verify the significance of these identified proteins in angiogenesis.
Main Methods:
- Integrated the human interactome with known angiogenesis-annotated proteins.
- Identified a set of 202 angiogenesis-associated proteins.
- Analyzed gene expression in endothelial cell lines after VEGF-A treatment.
Main Results:
- A significant fraction of the 202 identified proteins showed perturbed gene expression during angiogenesis.
- Observed differential expression patterns for HIF-1α and HIF-2α post-VEGF-A treatment.
- Identified specific proteins with increasing (HIF-1α, APP, HIV-1 tat interactive protein 2, MEF2C) and decreasing (endoglin, liprin β1, HIF-2α) expression.
Conclusions:
- The study identified novel angiogenesis-associated proteins, expanding our understanding of angiogenesis regulation.
- Findings suggest potential new therapeutic targets for angiogenesis-related diseases.
- The research also indicated a potential role for endothelial cells in Alzheimer's disease pathogenesis.
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