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Notch promotes vascular maturation by inducing integrin-mediated smooth muscle cell adhesion to the endothelial basement membrane

Academic Article
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Overview

authors

  • Scheppke, L.
  • Murphy, E. A.
  • Zarpellon, A.
  • Hofmann, J. J.
  • Merkulova, A.
  • Shields, D. J.
  • Weis, S. M.
  • Byzova, T. V.
  • Ruggeri, Zaverio
  • Iruela-Arispe, M. L.
  • Cheresh, D. A.

publication date

  • 2012

journal

  • Blood  Journal

abstract

  • Vascular development and angiogenesis initially depend on endothelial tip cell invasion, which is followed by a series of maturation steps, including lumen formation and recruitment of perivascular cells. Notch ligands expressed on the endothelium and their cognate receptors expressed on perivascular cells are involved in blood vessel maturation, though little is known regarding the Notch-dependent effectors that facilitate perivascular coverage of nascent vessels. Here, we report that vascular smooth muscle cell (VSMC) recognition of the Notch ligand Jagged1 on endothelial cells leads to expression of integrin αvβ3 on VSMCs. Once expressed, integrin αvβ3 facilitates VSMC adhesion to VWF in the endothelial basement membrane of developing retinal arteries, leading to vessel maturation. Genetic or pharmacologic disruption of Jagged1, Notch, αvβ3, or VWF suppresses VSMC coverage of nascent vessels and arterial maturation during vascular development. Therefore, we define a Notch-mediated interaction between the developing endothelium and VSMCs leading to adhesion of VSMCs to the endothelial basement membrane and arterial maturation.

subject areas

  • Animals
  • Arteries
  • Basement Membrane
  • Calcium-Binding Proteins
  • Cell Adhesion
  • Endothelial Cells
  • Endothelium, Vascular
  • Gene Expression Regulation
  • Humans
  • Integrins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Neovascularization, Physiologic
  • Protein Binding
  • RNA, Messenger
  • Receptors, Notch
  • Signal Transduction
  • von Willebrand Factor
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Identity

PubMed Central ID

  • PMC3311249

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2011-04-348706

PubMed ID

  • 22134168
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Additional Document Info

start page

  • 2149

end page

  • 2158

volume

  • 119

issue

  • 9

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