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Citation
Tags
HERO ID
571092
Reference Type
Journal Article
Title
Autocrine VEGF Signaling Is Required for Vascular Homeostasis
Author(s)
Lee, S; Chen, TT; Barber, CL; Jordan, MC; Murdock, J; Desai, S; Ferrara, N; Nagy, A; Roos, KP; Iruela-Arispe, ML
Year
2007
Is Peer Reviewed?
Yes
Journal
Cell
ISSN:
0092-8674
EISSN:
1097-4172
Volume
130
Issue
4
Page Numbers
691-703
DOI
10.1016/j.cell.2007.06.054
Abstract
Summary Vascular endothelial growth factor (VEGF) is essential for developmental and pathological angiogenesis. Here we show that in the absence of any pathological insult, autocrine VEGF is required for the homeostasis of blood vessels in the adult. Genetic deletion of vegf specifically in the endothelial lineage leads to progressive endothelial degeneration and sudden death in 55% of mutant mice by 25 weeks of age. The phenotype is manifested without detectable changes in the total levels of VEGF mRNA or protein, indicating that paracrine VEGF could not compensate for the absence of endothelial VEGF. Furthermore, wild-type, but not VEGF null, endothelial cells showed phosphorylation of VEGFR2 in the absence of exogenous VEGF. Activation of the receptor in wild-type cells was suppressed by small molecule antagonists but not by extracellular blockade of VEGF. These results reveal a cell-autonomous VEGF signaling pathway that holds significance for vascular homeostasis but is dispensable for the angiogenic cascade.
Keywords
CELLBIO; DEVBIO; HUMDISEASE
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