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

L Scheppke, EA Murphy, A Zarpellon… - Blood, The Journal …, 2012 - ashpublications.org
L Scheppke, EA Murphy, A Zarpellon, JJ Hofmann, A Merkulova, DJ Shields, SM Weis
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
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 Notchdependent effectors that facilitate perivascular coverage of
nascent vessels. Here, we report that vascular smooth muscle cell (VSMC) recognition of the …
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 Notchdependent 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.
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