Premium
A potential role for autocrine VEGF signaling in endothelial cell function
Author(s) -
Nwadozi Emmanuel,
Uchida Cassandra,
Gee Eric,
Liu Sammy T.K.,
Haas Tara L.
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.685.14
Subject(s) - autocrine signalling , paracrine signalling , vascular endothelial growth factor , vascular endothelial growth factor a , endothelial stem cell , microbiology and biotechnology , angiogenesis , vascular endothelial growth factor b , biology , chemistry , cancer research , cell culture , vegf receptors , receptor , in vitro , biochemistry , genetics
Paracrine‐derived vascular endothelial growth factor (VEGF) is established as an indispensable contributor to the angiogenic cascade. Autocrine VEGF, in contrast, is solely attributed to endothelial cell survival signaling, and its potential regulation of other endothelial cell functions has not been studied. We hypothesized that the deletion of VEGF would disrupt endothelial cell migration and shear stress adaptation. Endothelial cells were isolated from transgenic mice having VEGF exon 3 flanked by loxP sites (VEGF L/L ). Cells were transduced with adeno‐Cre recombinase to induce VEGF deletion, or adeno‐β‐galactosidase as a control. When subjected to a scrape migration assay, cells with Cre induced VEGF deletion (VEGFΔ) exhibited impaired cell motility compared VEGF L/L cells (12% compared to 64% wound closure after 48 hours; p<0.05). Shear stress stimulation (15 dynes; 2hr) caused significant increases in phospho‐Akt in VEGF L/L cells, which was repressed in VEGFΔ cells (2.4 vs. 1.5 fold above static, respectively). Shear‐induced increases in phospho‐p38MAPK were unaltered in VEGFΔ cells (3.9 vs 3.3 fold above static, respectively). Shear‐induced endothelial cell alignment (15 dynes; 24hr) also was repressed in VEGFΔ cells. Taken together these results provide novel evidence that autocrine VEGF contributes to multiple aspects of endothelial cell function.