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PMID: 18259607 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats.

The Journal of clinical investigation ·Vol. 118 ·No. 3 ·2008-03-00 ·Pages 913-23

Li Y, Zhang F, Nagai N, Tang Z, Zhang S, Scotney P, Lennartsson J, Zhu C, Qu Y, Fang C, Hua J, Matsuo O, Fong GH, Ding H, Cao Y, Becker KG, Nash A, Heldin CH, Li X

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.

MeSH Terms
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
Chemicals
Vascular Endothelial Growth Factor B Vascular Endothelial Growth Factor Receptor-1
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Li Yang
National Eye Institute, NIH, Porter Neuroscience Research Center, Bethesda, Maryland 20892, USA.
Zhang Fan
Nagai Nobuo
Tang Zhongshu
Zhang Shuihua
Scotney Pierre
Lennartsson Johan
Zhu Chaoyong
Qu Yi
Fang Changge
Hua Jianyuan
Matsuo Osamu
Fong Guo-Hua
Ding Hao
Cao Yihai
Becker Kevin G
Nash Andrew
Heldin Carl-Henrik
Li Xuri
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI33673
Published
2008-03-00
Pages
913-23
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC2230661
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1172/JCI33673 PMC Full Text View journal details
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