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.
Zhang
Fan
F
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tang
Zhongshu
Z
Hou
Xu
X
Lennartsson
Johan
J
Li
Yang
Y
Koch
Alexander W
AW
Scotney
Pierre
P
Lee
Chunsik
C
Arjunan
Pachiappan
P
Dong
Lijin
L
Kumar
Anil
A
Rissanen
Tuomas T
TT
Wang
Bin
B
Nagai
Nobuo
N
Fons
Pierre
P
Fariss
Robert
R
Zhang
Yongqing
Y
Wawrousek
Eric
E
Tansey
Ginger
G
Raber
James
J
Fong
Guo-Hua
GH
Ding
Hao
H
Greenberg
David A
DA
Becker
Kevin G
KG
Herbert
Jean-Marc
JM
Nash
Andrew
A
Yla-Herttuala
Seppo
S
Cao
Yihai
Y
Watts
Ryan J
RJ
Li
Xuri
X
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