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

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Book cover Biophysical Regulation of Vascular Differentiation and Assembly

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, MA415 Medical Sciences Building, Columbia, MO, 65212, USA

    George E. Davis

  2. Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, 65212, USA

    George E. Davis

  3. Dalton Cardiovascular Sciences Center, Columbia, MO, 65212, USA

    George E. Davis

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Davis, G.E., Stratman, A.N., Sacharidou, A. (2011). Molecular Control of Vascular Tube Morphogenesis and Stabilization: Regulation by Extracellular Matrix, Matrix Metalloproteinases, and Endothelial Cell–Pericyte Interactions. In: Gerecht, S. (eds) Biophysical Regulation of Vascular Differentiation and Assembly. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7835-6_2

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