Molecular Control of Vascular Tube Morphogenesis and Stabilization: Regulation by Extracellular Matrix, Matrix Metalloproteinases, and Endothelial Cell–Pericyte Interactions

  • George E. Davis
  • Amber N. Stratman
  • Anastasia Sacharidou
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


Recent studies have revealed a critical role for both extracellular matrices and matrix metalloproteinases in the molecular control of vascular morphogenesis and stabilization in three-dimensional (3D) tissue environments. Key interactions involve endothelial cells (ECs) and pericytes, which coassemble to affect vessel formation, remodeling, and stabilization events during development and postnatal life. EC–pericyte interactions control extracellular matrix remodeling events including vascular basement membrane matrix assembly, a necessary step for endothelial tube maturation and stabilization. ECs form tube networks in 3D extracellular matrices in a manner dependent on integrins, membrane-type metalloproteinases, and the Rho GTPases, Cdc42 and Rac1. Recent work has defined an EC lumen signaling complex of proteins composed of these proteins that controls 3D matrix-specific signaling events required for these processes. The EC tube formation process results in the creation of a network of proteolytically generated vascular guidance tunnels. These tunnels are physical matrix spaces that regulate vascular tube remodeling and represent matrix conduits into which pericytes are recruited to allow dynamic cell–cell interactions with ECs. These dynamic EC–pericyte interactions induce vascular basement membrane matrix deposition, leading to vessel maturation and stabilization.


Mural Cell Lumen Formation Vascular Tube Endothelial Cell Tube Vascular Regression 
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.



This work was supported by NIH grants HL79460, HL59373, and HL87308 to G.E. Davis. A.N. Stratman was supported by a AHA predoctoral fellowship #09PRE2140028.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • George E. Davis
    • 1
    • 2
    • 3
  • Amber N. Stratman
  • Anastasia Sacharidou
  1. 1.Department of Medical Pharmacology and PhysiologyUniversity of Missouri School of MedicineColumbiaUSA
  2. 2.Department of Pathology and Anatomical SciencesUniversity of Missouri School of MedicineColumbiaUSA
  3. 3.Dalton Cardiovascular Sciences CenterColumbiaUSA

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