Premium
Wnt5a inhibits angiogenic function via soluble VEGF receptor 1 expression in human microvascular endothelial cells
Author(s) -
Shuler Michaela M,
Murdoch Colin E,
Cohen Richard A,
Matsui Reiko
Publication year - 2013
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/fasebj.27.1_supplement.688.4
Subject(s) - autocrine signalling , paracrine signalling , angiogenesis , microbiology and biotechnology , vascular endothelial growth factor , vascular endothelial growth inhibitor , endothelial stem cell , vascular endothelial growth factor b , wnt signaling pathway , vascular endothelial growth factor a , wnt5a , biology , receptor , cancer research , chemistry , signal transduction , biochemistry , vegf receptors , in vitro
Alternative splicing of the gene encoding vascular endothelial growth factor receptor 1(VEGFR1/FLT1) generates an anti‐angiogenic soluble form (sVEGFR1/sFLT). sVEGFR1 has a high affinity for VEGF‐A and can act as a decoy receptor, preventing signaling through the pro‐angiogenic VEGFR2 receptor. Regulation of sVEGFR1 expression in endothelial cells is not fully understood. Herein we show that the non‐canonical Wnt ligand, Wnt5a, attenuates endothelial function through regulation of sVEGFR1. Recombinant Wnt5a induced rapid and sustained expression of the soluble form of VEGFR1 in human cardiac microvascular endothelial cells. In accordance, Wnt5a treatment inhibited VEGF‐induced endothelial migration and tube formation, as well as attenuating endothelial cell proliferation. sVEGFR1 expression in endothelial cells was downregulated by Box5, a Wnt5a competitive antagonist. Wnt5a regulation of VEGFR1 has been implicated in myeloid cells. Since both inflammatory and endothelial cells release Wnt5a, our data suggests Wnt5a may be important in the autocrine and paracrine signals contributing to endothelial dysregulation. These findings provide a new understanding in physiological and pathological regulation of VEGF‐induced angiogenesis. (R37 HL104017)