TY - JOUR
T1 - VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis
AU - Zhang, Fan
AU - Tang, Zhongshu
AU - Hou, Xu
AU - Lennartsson, Johan
AU - Li, Yang
AU - Koch, Alexander W.
AU - Scotney, Pierre
AU - Lee, Chunsik
AU - Arjunan, Pachiappan
AU - Dong, Lijin
AU - Kumar, Anil
AU - Rissanen, Tuomas T.
AU - Wang, Bin
AU - Nagai, Nobuo
AU - Fons, Pierre
AU - Fariss, Robert
AU - Zhang, Yongqing
AU - Wawrousek, Eric
AU - Tansey, Ginger
AU - Raber, James
AU - Fong, Guo Hua
AU - Ding, Hao
AU - Greenberg, David A.
AU - Becker, Kevin G.
AU - Herbert, Jean Marc
AU - Nash, Andrew
AU - Yla-Herttuala, Seppo
AU - Cao, Yihai
AU - Watts, Ryan J.
AU - Lia, Xuri
PY - 2009/4/14
Y1 - 2009/4/14
N2 - VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a "survival," rather than an "angiogenic" factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
AB - VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a "survival," rather than an "angiogenic" factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
KW - Apoptosis
KW - Ocular neovascularization
KW - Vascular survival
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U2 - 10.1073/pnas.0813061106
DO - 10.1073/pnas.0813061106
M3 - Article
C2 - 19369214
AN - SCOPUS:65549139264
SN - 0027-8424
VL - 106
SP - 6152
EP - 6157
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -