Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis

PLoS One. 2011;6(9):e24887. doi: 10.1371/journal.pone.0024887. Epub 2011 Sep 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Antigens, CD / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Line
  • Endoglin
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • MADS Domain Proteins / metabolism
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors / metabolism
  • Neovascularization, Pathologic / metabolism*
  • Receptors, Cell Surface / metabolism
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Basic Helix-Loop-Helix Transcription Factors
  • ENG protein, human
  • Endoglin
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Myogenic Regulatory Factors
  • PPFIBP1 protein, human
  • Receptors, Cell Surface
  • Vascular Endothelial Growth Factor A
  • endothelial PAS domain-containing protein 1