Abstract |
Despite its early discovery and high sequence homology to the other VEGF family members, the biological functions of VEGF-B remain poorly understood. We revealed here a novel function for VEGF-B as a potent inhibitor of apoptosis. Using gene expression profiling of mouse primary aortic smooth muscle cells, and confirming the results by real-time PCR using mouse and rat cell lines, we showed that VEGF-B inhibited the expression of genes encoding the proapoptotic BH3-only proteins and other apoptosis- and cell death-related proteins, including p53 and members of the caspase family, via activation of VEGFR-1. Consistent with this, VEGF-B treatment rescued neurons from apoptosis in the retina and brain in mouse models of ocular neurodegenerative disorders and stroke, respectively. Interestingly, VEGF-B treatment at the dose effective for neuronal survival did not cause retinal neovascularization, suggesting that VEGF-B is the first member of the VEGF family that has a potent antiapoptotic effect while lacking a general angiogenic activity. These findings indicate that VEGF-B may potentially offer a new therapeutic option for the treatment of neurodegenerative diseases.
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Authors | Yang Li, Fan Zhang, Nobuo Nagai, Zhongshu Tang, Shuihua Zhang, Pierre Scotney, Johan Lennartsson, Chaoyong Zhu, Yi Qu, Changge Fang, Jianyuan Hua, Osamu Matsuo, Guo-Hua Fong, Hao Ding, Yihai Cao, Kevin G Becker, Andrew Nash, Carl-Henrik Heldin, Xuri Li |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 118
Issue 3
Pg. 913-23
(Mar 2008)
ISSN: 0021-9738 [Print] United States |
PMID | 18259607
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Vascular Endothelial Growth Factor B
- Vascular Endothelial Growth Factor Receptor-1
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Topics |
- Animals
- Apoptosis
(drug effects)
- Cells, Cultured
- Female
- Gene Expression Regulation
(drug effects)
- Humans
- Mice
- Neovascularization, Physiologic
(drug effects)
- Oxidative Stress
(drug effects)
- Rats
- Retina
(metabolism)
- Vascular Endothelial Growth Factor B
(pharmacology)
- Vascular Endothelial Growth Factor Receptor-1
(physiology)
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