Laminin-Binding Integrins Induce Dll4 Expression and Notch Signaling in Endothelial Cells

Estrach, Soline; Cailleteau, Laurence; Franco, Cláudio A.; Gerhardt, Holger; Stefani, Caroline; Lemichez, Emmanuel; Gagnoux‐Palacios, Laurent; Meneguzzi, Guerríno; Mettouchi, Amel

doi:10.1161/circresaha.111.240622

Cited by 104 publications

(86 citation statements)

References 45 publications

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“…Our data further suggest that VEGFR2 activates and that VEGFR3/Notch signaling suppresses filopodia extension in endothelial cells. On the other hand, the relative increase in DLL4 and filopodia projections observed in the Vegfr2 iΔEC retinas after Notch inhibition emphasizes the existence of other tip cell regulators, such as laminins, in the angiogenic microenvironment (38,39) (Fig. S5).…”

Section: Discussionmentioning

confidence: 98%

VEGFR3 does not sustain retinal angiogenesis without VEGFR2

Zarkada

Heinolainen

Mäkinen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

113

103

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Angiogenesis, the formation of new blood vessels, is regulated by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). VEGFR2 is abundant in the tip cells of angiogenic sprouts, where VEGF/VEGFR2 functions upstream of the delta-like ligand 4 (DLL4)/Notch signal transduction pathway. VEGFR3 is expressed in all endothelia and is indispensable for angiogenesis during early embryonic development. In adults, VEGFR3 is expressed in angiogenic blood vessels and some fenestrated endothelia. VEGFR3 is abundant in endothelial tip cells, where it activates Notch signaling, facilitating the conversion of tip cells to stalk cells during the stabilization of vascular branches. Subsequently, Notch activation suppresses VEGFR3 expression in a negative feedback loop. Here we used conditional deletions and a Notch pathway inhibitor to investigate the cross-talk between VEGFR2, VEGFR3, and Notch in vivo. We show that postnatal angiogenesis requires VEGFR2 signaling also in the absence of Notch or VEGFR3, and that even small amounts of VEGFR2 are able to sustain angiogenesis to some extent. We found that VEGFR2 is required independently of VEGFR3 for endothelial DLL4 up-regulation and angiogenic sprouting, and for VEGFR3 functions in angiogenesis. In contrast, VEGFR2 deletion had no effect, whereas VEGFR3 was essential for postnatal lymphangiogenesis, and even for lymphatic vessel maintenance in adult skin. Knowledge of these interactions and the signaling functions of VEGFRs in blood vessels and lymphatic vessels is essential for the therapeutic manipulation of the vascular system, especially when considering multitargeted antiangiogenic treatments.

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Section: Discussionmentioning

confidence: 98%

VEGFR3 does not sustain retinal angiogenesis without VEGFR2

Zarkada

Heinolainen

Mäkinen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

113

103

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“…These include cell-cell interactions (Stratman and Davis, 2012), cell interactions with the surrounding ECM through specific cell-adhesion molecules (Estrach et al, 2011) and cell signaling via secreted or ECM-sequestered GFs or cytokines (Stratman et al, 2011). Other physicochemical parameters include proteolytic matrix remodeling and matrix stiffness, which affect vascular morphogenesis and network formation Busnadiego et al, 2013;Turturro et al, 2013).…”

Section: Vascular Development and Engineering Parametersmentioning

confidence: 99%

“…The ECMs present during vascular differentiation and development are mainly composed of fibronectin, laminin, collagen and hyaluronic acid (HA) (Nelson and Bissell, 2006;Estrach et al, 2011;Kashima et al, 2013). The ECM not only provides a structural framework to support cellular function, but also regulates cellular behavior, including adhesion, proliferation, migration and differentiation of vascular cells through both cell-to-cell and cell-to-matrix interactions.…”

Section: The Vascular Ecmmentioning

confidence: 99%

Harnessing developmental processes for vascular engineering and regeneration

Park

Gerecht

2014

Development

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The formation of vasculature is essential for tissue maintenance and regeneration. During development, the vasculature forms via the dual processes of vasculogenesis and angiogenesis, and is regulated at multiple levels: from transcriptional hierarchies and protein interactions to inputs from the extracellular environment. Understanding how vascular formation is coordinated in vivo can offer valuable insights into engineering approaches for therapeutic vascularization and angiogenesis, whether by creating new vasculature in vitro or by stimulating neovascularization in vivo. In this Review, we will discuss how the process of vascular development can be used to guide approaches to engineering vasculature. Specifically, we will focus on some of the recently reported approaches to stimulate therapeutic angiogenesis by recreating the embryonic vascular microenvironment using biomaterials for vascular engineering and regeneration.

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“…During sprouting angiogenesis, endothelial cells (ECs) secrete matrix proteins such as vitronectin, fibronectin, and collagen I leading to the formation of a provisional ECM, which sustains ECs proliferation and migration (2). Moreover, ECM proteins coordinate or at least complement the sprouting process by modulating the differentiation of the so-called tip and stalk cells (3,4). When the angiogenic stimulus drops, ECs arrest the migration and proliferation processes, form a lumen, and re-establish functional VE-cadherin-mediated cell-to-cell adherens junctions (5).…”

mentioning

confidence: 99%

Neuroligin 1 Induces Blood Vessel Maturation by Cooperating with the α6 Integrin

Samarelli

Riccitelli

Bizzozero

et al. 2014

Journal of Biological Chemistry

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Background: Disregulated adhesion of endothelial cells to extracellular matrix proteins is associated with numerous human diseases. Results: Neuroligin 1 modulates the interaction between ␣6 integrin and laminin and induces the formation of a normal extracellular matrix. Conclusion: Neuroligin 1 modulates vessel maturation and cell adhesion. Significance: We first report that Neuroligin 1, originally a synaptic protein, modulates extracellular matrix functions in the vascular system.

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Laminin-Binding Integrins Induce Dll4 Expression and Notch Signaling in Endothelial Cells

Cited by 104 publications

References 45 publications

VEGFR3 does not sustain retinal angiogenesis without VEGFR2

VEGFR3 does not sustain retinal angiogenesis without VEGFR2

Harnessing developmental processes for vascular engineering and regeneration

Neuroligin 1 Induces Blood Vessel Maturation by Cooperating with the α6 Integrin

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