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

Fan Zhang, Zhongshu Tang, Xu Hou, Johan Lennartsson, Yang Li, Alexander W. Koch, Pierre Scotney, Chunsik Lee, Pachiappan Arjunan, Lijin Dong, Anil Kumar, Tuomas T. Rissanen, Bin Wang, Nobuo Nagai, Pierre Fons, Robert Fariss, Yongqing Zhang, Eric Wawrousek, Ginger Tansey, James RaberGuo Hua Fong, Hao Ding, David A. Greenberg, Kevin G. Becker, Jean Marc Herbert, Andrew Nash, Seppo Yla-Herttuala, Yihai Cao, Ryan J. Watts, Xuri Lia

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6152-6157
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number15
DOIs
StatePublished - Apr 14 2009

Keywords

  • Apoptosis
  • Ocular neovascularization
  • Vascular survival

ASJC Scopus subject areas

  • General

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