Quantification and cell-to-cell variation of vascular endothelial growth factor receptors

Exp Cell Res. 2011 Apr 15;317(7):955-65. doi: 10.1016/j.yexcr.2010.12.014. Epub 2010 Dec 23.

Abstract

The vascular endothelial growth factor receptors (VEGFR) play a significant role in angiogenesis, the formation of new blood vessels from existing vasculature. Systems biology offers promising approaches to better understand angiogenesis by computational modeling the key molecular interactions in this process. Such modeling requires quantitative knowledge of cell surface density of pro-angiogenic receptors versus anti-angiogenic receptors, their regulation, and their cell-to-cell variability. Using quantitative fluorescence, we systematically characterized the endothelial surface density of VEGFRs and neuropilin-1 (NRP1). We also determined the role of VEGF in regulating the surface density of these receptors. Applying cell-by-cell analysis revealed heterogeneity in receptor surface density and VEGF tuning of this heterogeneity. Altogether, we determine inherent differences in the surface expression levels of these receptors and the role of VEGF in regulating the balance of anti-angiogenic or modulatory (VEGFR1) and pro-angiogenic (VEGFR2) receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Vessels / cytology
  • Blood Vessels / metabolism
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Humans
  • Models, Biological
  • Neovascularization, Physiologic
  • Neuropilin-1 / metabolism
  • Protein Isoforms / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism*
  • Vascular Endothelial Growth Factors / metabolism*

Substances

  • Protein Isoforms
  • Vascular Endothelial Growth Factors
  • Neuropilin-1
  • Receptors, Vascular Endothelial Growth Factor