Article

Analysis of VEGF-A Regulated Gene Expression in Endothelial Cells to Identify Genes Linked to Angiogenesis

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS ONE (Impact Factor: 3.23). 09/2011; 6(9):e24887. DOI: 10.1371/journal.pone.0024887
Source: PubMed

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.

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    • "Moreover, our data had shown that MEF2C is another factor specifically induced by VEGF-A and also bFGF, implicating MEF2C also in the control of angiogenesis [6], [11]. An important angiogenesis-related function of MEF2C was further corroborated by its demonstrated expression in tip cells [12], however its mechanism of action in endothelial cells during angiogenesis has not yet been fully determined. "
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