VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis

被引：237

作者：

Zhang, Fan ^{[1
]}

Tang, Zhongshu ^{[1
]}

Hou, Xu ^{[1
]}

Lennartsson, Johan ^{[2
]}

Li, Yang ^{[1
]}

Koch, Alexander W. ^{[3
]}

Scotney, Pierre ^{[4
]}

Lee, Chunsik ^{[1
]}

Arjunan, Pachiappan ^{[1
]}

Dong, Lijin ^{[1
]}

Kumar, Anil ^{[1
]}

Rissanen, Tuomas T. ^{[5
]}

Wang, Bin ^{[6
]}

Nagai, Nobuo ^{[7
]}

Fons, Pierre ^{[8
]}

Fariss, Robert ^{[1
]}

Zhang, Yongqing ^{[9
]}

Wawrousek, Eric ^{[1
]}

Tansey, Ginger ^{[1
]}

Raber, James ^{[1
]}

Fong, Guo-Hua ^{[10
]}

Ding, Hao ^{[11
]}

Greenberg, David A. ^{[12
]}

Becker, Kevin G. ^{[9
]}

Herbert, Jean-Marc ^{[8
]}

Nash, Andrew ^{[4
]}

Yla-Herttuala, Seppo ^{[5
]}

Cao, Yihai ^{[13
]}

Watts, Ryan J. ^{[3
]}

Li, Xuri ^{[1
]}

机构：

[1] NEI, NIH, Bethesda, MD 20892 USA

[2] Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden

[3] Genentech Inc, Prot Chem, Neurodegenerat Labs, San Francisco, CA 94080 USA

[4] CSL Ltd, Parkville, Vic 3052, Australia

[5] Univ Kuopio, Dept Biotechnol & Mol Med, FIN-70211 Kuopio, Finland

[6] Weifang Med Univ, Affiliated Hosp, Med Imaging Ctr, Dept Radiol, Weifang 261042, Peoples R China

[7] Kinki Univ, Sch Med, Dept Physiol, Osaka 5898511, Japan

[8] Sanofi Aventis Rech, Cardiovasc Thrombosis Res Dept, F-31036 Toulouse, France

[9] NIA, TRIAD Technol Ctr, NIH, Baltimore, MD 21224 USA

[10] Univ Connecticut, Ctr Vasc Biol, Farmington, CT 06030 USA

[11] Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB R3E 3P5, Canada

[12] Buck Inst Age Res, Novato, CA 94945 USA

[13] Karolinska Inst, Dept Microbiol, S-17177 Stockholm, Sweden

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 15期

基金：

美国国家卫生研究院;

关键词：

apoptosis; vascular survival; ocular neovascularization; FAMILY-MEMBERS; IN-VIVO; MICE; PERMEABILITY; LETHALITY; LACKING; LUNG;

D O I：

10.1073/pnas.0813061106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：6152 / 6157

页数：6

共 30 条

[1] Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect [J].