VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats.
2008 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, Vol. 118, no 3, 913-923 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 118, no 3, 913-923 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-15826DOI: 10.1172/JCI33673ISI: 000253646400016PubMedID: 18259607OAI: oai:DiVA.org:uu-15826DiVA: diva2:43597