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: 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)

Chemical References

• Vascular Endothelial Growth Factor B
• Vascular Endothelial Growth Factor Receptor-1

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)