Premium
Soluble forms of VEGF receptor‐1 and ‐2 promote vascular maturation via mural cell recruitment
Author(s) -
Lorquet Sophie,
Berndt Sarah,
Blacher Silvia,
Gengoux Emily,
Peulen Olivier,
Maquoi Erik,
Noël Agnès,
Foidart JeanMichel,
Munaut Carine,
Páqueux Christel
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-149070
Subject(s) - mural cell , angiogenesis , enos , microbiology and biotechnology , paracrine signalling , receptor , endothelial stem cell , ex vivo , chemistry , biology , cancer research , in vitro , endocrinology , biochemistry , nitric oxide , nitric oxide synthase
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 (ECs) and mural cells that leads to blood vessel stabilization. Through a multidisciplinary approach, we provide evidence that these soluble VEGF receptors promote mural cell migration through a paracrine mechanism involving interplay in ECs between VEGF/VEGFR‐2 and sphingosine1‐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 perform the following actions: 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 toward ECs, and 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, S., Berndt, S., Blacher, S., Gengoux, E., Peulen, O., Maquoi, E., Noël, A., Foidart, J.‐M., Munaut, C., Pèqueux, C. Soluble forms of VEGF receptor‐1 and ‐2 promote vascular maturation via mural cell recruitment. FASEB J. 24, 3782 ‐3795 (2010). www.fasebj.org