Journal
EXPERIMENTAL CELL RESEARCH
Volume 317, Issue 7, Pages 955-965Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2010.12.014
Keywords
Angiogenesis; Systems biology; VEGF; NRP1; Flow cytometry
Categories
Funding
- NIH [R01 HL101200, HL079653, R01 CA138264, T32 HL007581]
- UNCF/Merck
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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 VEGERs 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 heterogeneityi 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. (C) 2010 Elsevier Inc. All rights reserved.
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