VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats.
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.
Li
Yang
Y
National Eye Institute, NIH, Porter Neuroscience Research Center, Bethesda, Maryland 20892, USA.
Zhang
Fan
F
Nagai
Nobuo
N
Tang
Zhongshu
Z
Zhang
Shuihua
S
Scotney
Pierre
P
Lennartsson
Johan
J
Zhu
Chaoyong
C
Qu
Yi
Y
Fang
Changge
C
Hua
Jianyuan
J
Matsuo
Osamu
O
Fong
Guo-Hua
GH
Ding
Hao
H
Cao
Yihai
Y
Becker
Kevin G
KG
Nash
Andrew
A
Heldin
Carl-Henrik
CH
Li
Xuri
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D012160:Retina / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology*
D042561:Vascular Endothelial Growth Factor B; D040281:Vascular Endothelial Growth Factor Receptor-1