Autocrine VEGF Signaling Is Required for Vascular Homeostasis

Sunyoung Lee, Tom T. Chen, Chad L. Barber, Maria C. Jordan, Jared Murdock, Sharina Desai, Napoleone Ferrara, Andras Nagy, Kenneth P. Roos, M. Luisa Iruela-Arispe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)691-703
Number of pages13
JournalCell
Volume130
Issue number4
DOIs
Publication statusPublished - 24 Aug 2007
Externally publishedYes

Keywords

  • CELLBIO
  • DEVBIO
  • HUMDISEASE

Cite this

Lee, S., Chen, T. T., Barber, C. L., Jordan, M. C., Murdock, J., Desai, S., ... Iruela-Arispe, M. L. (2007). Autocrine VEGF Signaling Is Required for Vascular Homeostasis. Cell, 130(4), 691-703. https://doi.org/10.1016/j.cell.2007.06.054
Lee, Sunyoung ; Chen, Tom T. ; Barber, Chad L. ; Jordan, Maria C. ; Murdock, Jared ; Desai, Sharina ; Ferrara, Napoleone ; Nagy, Andras ; Roos, Kenneth P. ; Iruela-Arispe, M. Luisa. / Autocrine VEGF Signaling Is Required for Vascular Homeostasis. In: Cell. 2007 ; Vol. 130, No. 4. pp. 691-703.
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abstract = "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.",
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Lee, S, Chen, TT, Barber, CL, Jordan, MC, Murdock, J, Desai, S, Ferrara, N, Nagy, A, Roos, KP & Iruela-Arispe, ML 2007, 'Autocrine VEGF Signaling Is Required for Vascular Homeostasis' Cell, vol. 130, no. 4, pp. 691-703. https://doi.org/10.1016/j.cell.2007.06.054

Autocrine VEGF Signaling Is Required for Vascular Homeostasis. / Lee, Sunyoung; Chen, Tom T.; Barber, Chad L.; Jordan, Maria C.; Murdock, Jared; Desai, Sharina; Ferrara, Napoleone; Nagy, Andras; Roos, Kenneth P.; Iruela-Arispe, M. Luisa.

In: Cell, Vol. 130, No. 4, 24.08.2007, p. 691-703.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lee, Sunyoung

AU - Chen, Tom T.

AU - Barber, Chad L.

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AU - Desai, Sharina

AU - Ferrara, Napoleone

AU - Nagy, Andras

AU - Roos, Kenneth P.

AU - Iruela-Arispe, M. Luisa

PY - 2007/8/24

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N2 - 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.

AB - 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.

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Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S et al. Autocrine VEGF Signaling Is Required for Vascular Homeostasis. Cell. 2007 Aug 24;130(4):691-703. https://doi.org/10.1016/j.cell.2007.06.054