VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats.
J Clin Invest
; 118(3): 913-23, 2008 Mar.
Article
in En
| MEDLINE
| ID: mdl-18259607
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation
/
Apoptosis
/
Vascular Endothelial Growth Factor Receptor-1
/
Vascular Endothelial Growth Factor B
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Clin Invest
Year:
2008
Document type:
Article
Affiliation country:
United States