Angiogenesis

, Volume 11, Issue 2, pp 141–151

RGS5 expression is a quantitative measure of pericyte coverage of blood vessels

  • Tracy S. Mitchell
  • John Bradley
  • Gregory S. Robinson
  • David T. Shima
  • Yin-Shan Ng
Original Paper
  • 912 Downloads

Abstract

Pericytes play a key role in the process of vascular maturation and stabilization however, the current methods for quantifying pericyte coverage of the neovasculature are laborious and subjective in nature. In this study, we have developed an objective, sensitive, and high-throughput method for quantifying pericyte coverage of angiogenic vessels by analyzing the expression of the pericyte-specific gene, the regulator of G-protein signaling 5 (RGS5). We determined that RGS5 expression was up-regulated during a defined developmental time period in which nascent vessel sprouts acquired a pericyte covering. Furthermore, RGS5 expression was dramatically reduced in vessels with poor pericyte coverage compared to normal angiogenic vasculature. Finally, we determined that the susceptibility of nascent vessels to regression by vascular endothelial growth factor (VEGF) inhibition was significantly reduced following RGS5 up-regulation, further implicating RGS5 in pericyte-endothelial cell interactions and the vascular maturation process. These studies establish the use of RGS5 gene expression as a quantitative and robust measure of pericyte coverage of neovasculature. This method provides a tool for vascular biologists studying pericyte-endothelial cell interactions and vascular maturation in both normal and pathological conditions, such as diabetic retinopathy and cancer.

Keywords

Angiogenesis Endothelial cell Mural cell Pericyte RGS5 Vascular maturation Vascular smooth muscle Vascular stabilization 

Abbreviations

nRGS5

PECAM1-Normalized Regulator of G-protein signaling 5

PDGF-B

Platelet-derived growth factor-B

PDGFRβ

Platelet-derived growth factor receptor β

RGS5

Regulator of G-protein signaling 5

SMA

Smooth muscle actin

VEGF

Vascular endothelial growth factor, vascular permeability factor

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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Tracy S. Mitchell
    • 1
    • 2
  • John Bradley
    • 1
    • 3
  • Gregory S. Robinson
    • 1
    • 4
  • David T. Shima
    • 1
    • 5
  • Yin-Shan Ng
    • 1
    • 6
  1. 1.OSI EyetechLexingtonUSA
  2. 2.Adnexus TherapeuticsWalthamUSA
  3. 3.Institute for Nutrisciences and HealthCharlottetownCanada
  4. 4.Shire HGTCambridgeUSA
  5. 5.The Institute of OphthalmologyUniversity College LondonLondonUK
  6. 6.Pervasis TherapeuticsCambridgeUSA

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