VEGF-B: a survival, or an angiogenic factor?
Despite its early discovery and high sequence homology to the other VEGF family members, the biological function of VEGF-B remained debatable for a long time, and VEGF-B has received little attention from the field thus far. Recently, we and others have found that (1) VEGF-B is a potent survival factor for different types of cells by inhibiting apoptosis via suppressing the expression of BH3-only protein and other apoptotic/cell death-related genes. (2) VEGF-B has a negligible role in inducing blood vessel growth in most organs. Instead, it is critically required for blood vessel survival. VEGF-B targeting inhibited pathological angiogenesis by abolishing blood vessel survival in different animal models. (3) Using different types of neuro-injury and neurodegenerative disease models, VEGF-B treatment protected endangered neurons from apoptosis without inducing undesired blood vessel growth or permeability. Thus, VEGF-B is the first member of the VEGF family that has a potent survival/anti-apoptotic effect, while lacking a general angiogenic activity. Our work thus advocates that the major function of VEGF-B is to act as a "survival", rather than an "angiogenic" factor and implicates a therapeutic potential of VEGF-B in treating different types of vascular and neurodegenerative diseases.
Li
Xuri
X
National Eye Institute, National Institutes of Health, Bethesda, MD, USA. lixur@nei.nih.gov
Lee
Chunsik
C
Tang
Zhongshu
Z
Zhang
Fan
F
Arjunan
Pachiappan
P
Li
Yang
Y
Hou
Xu
X
Kumar
Anil
A
Dong
Lijin
L
D042501:Angiogenic Proteins / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D042561:Vascular Endothelial Growth Factor B / Q000502:physiology*
D042501:Angiogenic Proteins; D051017:Apoptosis Regulatory Proteins; D042561:Vascular Endothelial Growth Factor B
Clin Exp Ophthalmol. 2003 Feb;31(1):61-5
12580897
Nature. 1996 Apr 4;380(6573):439-42
8602242
Clin Exp Pharmacol Physiol. 2002 Nov;29(11):1035-9
12366398
J Vasc Res. 2009;46(1):45-54
18552506
Circulation. 2009 Feb 17;119(6):845-56
19188502
Nat Med. 2001 May;7(5):575-83
11329059
Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1614-20
18511699
J Cereb Blood Flow Metab. 2004 Oct;24(10):1146-52
15529014
Nat Med. 2002 Aug;8(8):831-40
12091877
Arthritis Rheum. 2003 Sep;48(9):2660-9
13130487
EMBO J. 1997 Jul 1;16(13):3898-911
9233800
Circ Res. 2000 Feb 4;86(2):E29-35
10666423
J Biol Chem. 1998 Nov 20;273(47):31273-82
9813035
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15859-64
14657382
Blood. 2008 Nov 1;112(9):3638-49
18664627
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6152-7
19369214
Cytokine. 2005 Dec 7;32(5):206-12
16289960
J Cell Biochem. 2007 Feb 15;100(3):727-37
17115409
Circulation. 2001 Jul 17;104(3):358-64
11457758
Pulm Pharmacol Ther. 2006;19(1):61-9
16286239
Oncogene. 1998 Jul 23;17(3):303-11
9690512
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11709-14
9751730
J Clin Invest. 2007 Nov;117(11):3188-97
17975666
Dev Dyn. 1999 May;215(1):12-25
10340753
Eur J Clin Invest. 2005 Nov;35(11):669-76
16269016
Biochem Biophys Res Commun. 2003 Feb 7;301(2):371-7
12565870
Circ Res. 2003 Jul 25;93(2):114-23
12805240
Nat Rev Cancer. 2008 Aug;8(8):632-45
18580951
Biochemistry. 2008 Mar 18;47(11):3345-51
18284215
PLoS One. 2007 Nov 14;2(11):e1161
18000534
Sci Signal. 2009 Feb 24;2(59):re1
19244214
J Invest Dermatol. 1998 Jul;111(1):1-6
9665379
Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1575-6
18716319
Growth Factors. 2001;19(1):49-59
11678209
Nature. 1996 Apr 4;380(6573):435-9
8602241
Int J Biochem Cell Biol. 2001 Apr;33(4):421-6
11312110
Science. 1997 May 30;276(5317):1423-5
9162011
Transplantation. 2002 Jun 15;73(11):1703-6
12084990
Angiogenesis. 2006;9(4):225-30; discussion 231
17109193
Blood. 2009 Apr 30;113(18):4468-75
19074006
Nat Immunol. 2004 Jan;5(1):74-80
14634646
Circ Res. 2003 May 30;92(10):1098-106
12714562
Circ Res. 2005 Sep 16;97(6):e60-70
16109918
Curr Opin Cell Biol. 2009 Apr;21(2):154-65
19230644
Cancer Cell. 2002 Feb;1(1):99-108
12086892
J Clin Invest. 2003 Jul;112(1):50-7
12840058
J Cell Sci. 2002 Jun 15;115(Pt 12):2559-67
12045226
Nat Rev Drug Discov. 2007 Apr;6(4):273-86
17396134
Am J Physiol Lung Cell Mol Physiol. 2003 Jun;284(6):L926-37
12547729
J Clin Invest. 2008 Mar;118(3):913-23
18259607
J Biol Chem. 2000 Sep 1;275(35):26690-5
10842181
Exp Cell Res. 2006 Mar 10;312(5):584-93
16445911
Genome Res. 1996 Feb;6(2):124-31
8919691
Nature. 2005 Dec 15;438(7070):946-53
16355212
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2576-81
8637916
Am J Pathol. 1995 May;146(5):1029-39
7538264
Nature. 2000 Sep 14;407(6801):249-57
11001068
Blood. 2003 Jul 1;102(1):161-8
12649136
Nature. 2005 Dec 15;438(7070):967-74
16355214
Hum Gene Ther. 2003 Oct 10;14(15):1451-62
14577925
Circ Res. 2008 Oct 24;103(9):1018-26
18757827
J Neurosci. 2008 Oct 15;28(42):10451-9
18923022