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Methodologic Approaches to Investigate Vascular Tube Morphogenesis and Maturation Events in 3D Extracellular Matrices In Vitro and In Vivo

  • Amber N. Stratman
  • Dae Joong Kim
  • Anastasia Sacharidou
  • Katherine R. Speichinger
  • George E. Davis
Chapter

Abstract

De novo blood vessel formation is regulated by two major processes, termed vasculogenesis and angiogenesis. A key aspect of this formation is the process of endothelial cell (EC) lumen and tube assembly. Major advances have been made in our understanding of the EC lumen formation process primarily through the development and utilization of in vitro models of this process in 3D extracellular matrices. Recent advances include the identification of an EC lumen signaling complex that controls EC tubulogenesis in 3D collagen matrices and determination of growth factor requirements that are required for these events under serum-free defined conditions. Components of the lumen signaling complex include the collagen-binding integrin, α2β1, the membrane-type 1 matrix metalloproteinase, MT1-MMP, junction adhesion molecules B and C, Par3, Par6b and the Rho GTPase, Cdc42. This complex of proteins controls EC lumen and tube formation and establishes the signaling conditions necessary to both form and sustain an EC tube network in 3D matrices. This EC tube network induces the recruitment of pericytes which then affect tube and extracellular matrix remodeling events to regulation the maturation of tubes. Methodologies utilized to address these events are presented to illustrate how the cellular and molecular basis for EC tube morphogenesis and stabilization are currently investigated.

Keywords

Tube Formation Stem Cell Factor Vascular Basement Membrane Vascular Morphogenesis Endothelial Cell Tube 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by NIH grants HL59373, HL79460, HL87308, and HL105606 to GED.

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Amber N. Stratman
    • 1
  • Dae Joong Kim
    • 1
  • Anastasia Sacharidou
    • 1
  • Katherine R. Speichinger
    • 1
  • George E. Davis
    • 2
    • 1
  1. 1.Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research CenterUniversity of Missouri School of MedicineColumbiaUSA
  2. 2.Department of Pathology and Anatomical Sciences, Dalton Cardiovascular Research CenterUniversity of Missouri School of MedicineColumbiaUSA

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