title: VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats.
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.
authors.affiliation: National Eye Institute, NIH, Porter Neuroscience Research Center, Bethesda, Maryland 20892, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nagai
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Tang
authors.forename: Shuihua
authors.initials: S
authors.lastname: Zhang
authors.forename: Pierre
authors.initials: P
authors.lastname: Scotney
authors.forename: Johan
authors.initials: J
authors.lastname: Lennartsson
authors.forename: Chaoyong
authors.initials: C
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.forename: Changge
authors.initials: C
authors.lastname: Fang
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Hua
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Fong
authors.forename: Hao
authors.initials: H
authors.lastname: Ding
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Andrew
authors.initials: A
authors.lastname: Nash
authors.forename: Carl-Henrik
authors.initials: CH
authors.lastname: Heldin
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
mesh_terms: 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*
chemical_list: D042561:Vascular Endothelial Growth Factor B; D040281:Vascular Endothelial Growth Factor Receptor-1