[en] Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF agents. Here, we report that these soluble receptors contribute to vessel maturation by mediating a dialogue between endothelial cells (EC) and mural cells that leads to blood vessel stabilization. Through a multidisciplinary approach, we provide evidences that these soluble VEGF receptors promote mural cell migration through a paracrine mechanism involving interplay in EC between VEGF/VEGFR-2 and sphingosine-1- phosphate type-1 (S1P)/S1P1 pathways that leads to endothelial nitric oxyde synthase (eNOS) activation. This new paradigm is supported by the finding that sVEGFR-1 and -2: 1) induce an eNOS-dependent outgrowth of a mural cell network in an ex vivo model of angiogenesis, 2) increase the mural cell coverage of neovessels in vitro and in vivo, 3) promote mural cell migration towards EC, 4) stimulate endothelial S1P1 overproduction and eNOS activation that promote the migration and the recruitment of neighboring mural cells. These findings provide new insights into mechanisms regulating physiological and pathological angiogenesis and vessel stabilization.
LORQUET, Sophie ; Centre Hospitalier Universitaire de Liège - CHU > Gynécologie-Obstétrique CHR
Berndt, Sarah
Blacher, Silvia ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Gengoux, Emily
Peulen, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Maquoi, Erik ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Munaut, Carine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Pequeux, Christel ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Language :
English
Title :
Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment.
Publication date :
2010
Journal title :
FASEB Journal
ISSN :
0892-6638
eISSN :
1530-6860
Publisher :
Federation of American Society for Experimental Biology, Bethesda, United States - Maryland
Volume :
24
Issue :
10
Pages :
3782-95
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.
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