VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis.
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.
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fan
F
Zhang
Zhongshu
Z
Tang
Xu
X
Hou
Johan
J
Lennartsson
Yang
Y
Li
Alexander W
AW
Koch
Pierre
P
Scotney
Chunsik
C
Lee
Pachiappan
P
Arjunan
Lijin
L
Dong
Anil
A
Kumar
Tuomas T
TT
Rissanen
Bin
B
Wang
Nobuo
N
Nagai
Pierre
P
Fons
Robert
R
Fariss
Yongqing
Y
Zhang
Eric
E
Wawrousek
Ginger
G
Tansey
James
J
Raber
Guo-Hua
GH
Fong
Hao
H
Ding
David A
DA
Greenberg
Kevin G
KG
Becker
Jean-Marc
JM
Herbert
Andrew
A
Nash
Seppo
S
Yla-Herttuala
Yihai
Y
Cao
Ryan J
RJ
Watts
Xuri
X
Li
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D016678:Genome; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D051381:Rats; D012160:Retina / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation; D042561:Vascular Endothelial Growth Factor B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D042561:Vascular Endothelial Growth Factor B