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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis</title><author><name sortKey="Zhang, Fan" sort="Zhang, Fan" uniqKey="Zhang F" first="Fan" last="Zhang">Fan Zhang</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Tang, Zhongshu" sort="Tang, Zhongshu" uniqKey="Tang Z" first="Zhongshu" last="Tang">Zhongshu Tang</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Hou, Xu" sort="Hou, Xu" uniqKey="Hou X" first="Xu" last="Hou">Xu Hou</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Lennartsson, Johan" sort="Lennartsson, Johan" uniqKey="Lennartsson J" first="Johan" last="Lennartsson">Johan Lennartsson</name><affiliation><nlm:aff id="aff2">Ludwig Institute for Cancer Research, Uppsala University, SE-751 24 Uppsala, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Li, Yang" sort="Li, Yang" uniqKey="Li Y" first="Yang" last="Li">Yang Li</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Koch, Alexander W" sort="Koch, Alexander W" uniqKey="Koch A" first="Alexander W." last="Koch">Alexander W. Koch</name><affiliation><nlm:aff id="aff3">Neurodegeneration Labs, Protein Chemistry, Genentech, Inc. San Francisco, CA 94080;</nlm:aff></affiliation></author><author><name sortKey="Scotney, Pierre" sort="Scotney, Pierre" uniqKey="Scotney P" first="Pierre" last="Scotney">Pierre Scotney</name><affiliation><nlm:aff id="aff4">CSL Limited, Parkville, Victoria 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Lee, Chunsik" sort="Lee, Chunsik" uniqKey="Lee C" first="Chunsik" last="Lee">Chunsik Lee</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Arjunan, Pachiappan" sort="Arjunan, Pachiappan" uniqKey="Arjunan P" first="Pachiappan" last="Arjunan">Pachiappan Arjunan</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Dong, Lijin" sort="Dong, Lijin" uniqKey="Dong L" first="Lijin" last="Dong">Lijin Dong</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Kumar, Anil" sort="Kumar, Anil" uniqKey="Kumar A" first="Anil" last="Kumar">Anil Kumar</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Rissanen, Tuomas T" sort="Rissanen, Tuomas T" uniqKey="Rissanen T" first="Tuomas T." last="Rissanen">Tuomas T. Rissanen</name><affiliation><nlm:aff id="aff5">Department of Biotechnology and Molecular Medicine, University of Kuopio, FIN-70211, Kuopio, Finland;</nlm:aff></affiliation></author><author><name sortKey="Wang, Bin" sort="Wang, Bin" uniqKey="Wang B" first="Bin" last="Wang">Bin Wang</name><affiliation><nlm:aff id="aff6">Department of Radiology, Medical Imaging Centre of the Affiliated Hospital, Weifang Medical University, Weifang 261042, China;</nlm:aff></affiliation></author><author><name sortKey="Nagai, Nobuo" sort="Nagai, Nobuo" uniqKey="Nagai N" first="Nobuo" last="Nagai">Nobuo Nagai</name><affiliation><nlm:aff id="aff7">Department of Physiology, Kinki University School of Medicine, Osaka 589-8511, Japan;</nlm:aff></affiliation></author><author><name sortKey="Fons, Pierre" sort="Fons, Pierre" uniqKey="Fons P" first="Pierre" last="Fons">Pierre Fons</name><affiliation><nlm:aff id="aff8">Sanofi-Aventis Recherche, Cardiovascular-Thrombosis Research Department, 31036 Toulouse Cedex, France;</nlm:aff></affiliation></author><author><name sortKey="Fariss, Robert" sort="Fariss, Robert" uniqKey="Fariss R" first="Robert" last="Fariss">Robert Fariss</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Zhang, Yongqing" sort="Zhang, Yongqing" uniqKey="Zhang Y" first="Yongqing" last="Zhang">Yongqing Zhang</name><affiliation><nlm:aff id="aff9">TRIAD Technology Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;</nlm:aff></affiliation></author><author><name sortKey="Wawrousek, Eric" sort="Wawrousek, Eric" uniqKey="Wawrousek E" first="Eric" last="Wawrousek">Eric Wawrousek</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Tansey, Ginger" sort="Tansey, Ginger" uniqKey="Tansey G" first="Ginger" last="Tansey">Ginger Tansey</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Raber, James" sort="Raber, James" uniqKey="Raber J" first="James" last="Raber">James Raber</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Fong, Guo Hua" sort="Fong, Guo Hua" uniqKey="Fong G" first="Guo-Hua" last="Fong">Guo-Hua Fong</name><affiliation><nlm:aff id="aff10">Center for Vascular Biology, University of Connecticut, Farmington, CT 06030;</nlm:aff></affiliation></author><author><name sortKey="Ding, Hao" sort="Ding, Hao" uniqKey="Ding H" first="Hao" last="Ding">Hao Ding</name><affiliation><nlm:aff id="aff11">Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada MB R3E 3P5;</nlm:aff></affiliation></author><author><name sortKey="Greenberg, David A" sort="Greenberg, David A" uniqKey="Greenberg D" first="David A." last="Greenberg">David A. Greenberg</name><affiliation><nlm:aff wicri:cut="; and" id="aff12">Buck Institute for Age Research, Novato, CA 94945</nlm:aff></affiliation></author><author><name sortKey="Becker, Kevin G" sort="Becker, Kevin G" uniqKey="Becker K" first="Kevin G." last="Becker">Kevin G. Becker</name><affiliation><nlm:aff id="aff9">TRIAD Technology Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;</nlm:aff></affiliation></author><author><name sortKey="Herbert, Jean Marc" sort="Herbert, Jean Marc" uniqKey="Herbert J" first="Jean-Marc" last="Herbert">Jean-Marc Herbert</name><affiliation><nlm:aff id="aff8">Sanofi-Aventis Recherche, Cardiovascular-Thrombosis Research Department, 31036 Toulouse Cedex, France;</nlm:aff></affiliation></author><author><name sortKey="Nash, Andrew" sort="Nash, Andrew" uniqKey="Nash A" first="Andrew" last="Nash">Andrew Nash</name><affiliation><nlm:aff id="aff4">CSL Limited, Parkville, Victoria 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Yla Herttuala, Seppo" sort="Yla Herttuala, Seppo" uniqKey="Yla Herttuala S" first="Seppo" last="Yla-Herttuala">Seppo Yla-Herttuala</name><affiliation><nlm:aff id="aff5">Department of Biotechnology and Molecular Medicine, University of Kuopio, FIN-70211, Kuopio, Finland;</nlm:aff></affiliation></author><author><name sortKey="Cao, Yihai" sort="Cao, Yihai" uniqKey="Cao Y" first="Yihai" last="Cao">Yihai Cao</name><affiliation><nlm:aff id="aff13">Department of Microbiology, Karolinska Institute, 171 77 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Watts, Ryan J" sort="Watts, Ryan J" uniqKey="Watts R" first="Ryan J." last="Watts">Ryan J. Watts</name><affiliation><nlm:aff id="aff3">Neurodegeneration Labs, Protein Chemistry, Genentech, Inc. San Francisco, CA 94080;</nlm:aff></affiliation></author><author><name sortKey="Li, Xuri" sort="Li, Xuri" uniqKey="Li X" first="Xuri" last="Li">Xuri Li</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19369214</idno><idno type="pmc">2669337</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669337</idno><idno type="RBID">PMC:2669337</idno><idno type="doi">10.1073/pnas.0813061106</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">001B27</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B27</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis</title><author><name sortKey="Zhang, Fan" sort="Zhang, Fan" uniqKey="Zhang F" first="Fan" last="Zhang">Fan Zhang</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Tang, Zhongshu" sort="Tang, Zhongshu" uniqKey="Tang Z" first="Zhongshu" last="Tang">Zhongshu Tang</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Hou, Xu" sort="Hou, Xu" uniqKey="Hou X" first="Xu" last="Hou">Xu Hou</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Lennartsson, Johan" sort="Lennartsson, Johan" uniqKey="Lennartsson J" first="Johan" last="Lennartsson">Johan Lennartsson</name><affiliation><nlm:aff id="aff2">Ludwig Institute for Cancer Research, Uppsala University, SE-751 24 Uppsala, Sweden;</nlm:aff></affiliation></author><author><name sortKey="Li, Yang" sort="Li, Yang" uniqKey="Li Y" first="Yang" last="Li">Yang Li</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Koch, Alexander W" sort="Koch, Alexander W" uniqKey="Koch A" first="Alexander W." last="Koch">Alexander W. Koch</name><affiliation><nlm:aff id="aff3">Neurodegeneration Labs, Protein Chemistry, Genentech, Inc. San Francisco, CA 94080;</nlm:aff></affiliation></author><author><name sortKey="Scotney, Pierre" sort="Scotney, Pierre" uniqKey="Scotney P" first="Pierre" last="Scotney">Pierre Scotney</name><affiliation><nlm:aff id="aff4">CSL Limited, Parkville, Victoria 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Lee, Chunsik" sort="Lee, Chunsik" uniqKey="Lee C" first="Chunsik" last="Lee">Chunsik Lee</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Arjunan, Pachiappan" sort="Arjunan, Pachiappan" uniqKey="Arjunan P" first="Pachiappan" last="Arjunan">Pachiappan Arjunan</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Dong, Lijin" sort="Dong, Lijin" uniqKey="Dong L" first="Lijin" last="Dong">Lijin Dong</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Kumar, Anil" sort="Kumar, Anil" uniqKey="Kumar A" first="Anil" last="Kumar">Anil Kumar</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Rissanen, Tuomas T" sort="Rissanen, Tuomas T" uniqKey="Rissanen T" first="Tuomas T." last="Rissanen">Tuomas T. Rissanen</name><affiliation><nlm:aff id="aff5">Department of Biotechnology and Molecular Medicine, University of Kuopio, FIN-70211, Kuopio, Finland;</nlm:aff></affiliation></author><author><name sortKey="Wang, Bin" sort="Wang, Bin" uniqKey="Wang B" first="Bin" last="Wang">Bin Wang</name><affiliation><nlm:aff id="aff6">Department of Radiology, Medical Imaging Centre of the Affiliated Hospital, Weifang Medical University, Weifang 261042, China;</nlm:aff></affiliation></author><author><name sortKey="Nagai, Nobuo" sort="Nagai, Nobuo" uniqKey="Nagai N" first="Nobuo" last="Nagai">Nobuo Nagai</name><affiliation><nlm:aff id="aff7">Department of Physiology, Kinki University School of Medicine, Osaka 589-8511, Japan;</nlm:aff></affiliation></author><author><name sortKey="Fons, Pierre" sort="Fons, Pierre" uniqKey="Fons P" first="Pierre" last="Fons">Pierre Fons</name><affiliation><nlm:aff id="aff8">Sanofi-Aventis Recherche, Cardiovascular-Thrombosis Research Department, 31036 Toulouse Cedex, France;</nlm:aff></affiliation></author><author><name sortKey="Fariss, Robert" sort="Fariss, Robert" uniqKey="Fariss R" first="Robert" last="Fariss">Robert Fariss</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Zhang, Yongqing" sort="Zhang, Yongqing" uniqKey="Zhang Y" first="Yongqing" last="Zhang">Yongqing Zhang</name><affiliation><nlm:aff id="aff9">TRIAD Technology Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;</nlm:aff></affiliation></author><author><name sortKey="Wawrousek, Eric" sort="Wawrousek, Eric" uniqKey="Wawrousek E" first="Eric" last="Wawrousek">Eric Wawrousek</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Tansey, Ginger" sort="Tansey, Ginger" uniqKey="Tansey G" first="Ginger" last="Tansey">Ginger Tansey</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Raber, James" sort="Raber, James" uniqKey="Raber J" first="James" last="Raber">James Raber</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author><author><name sortKey="Fong, Guo Hua" sort="Fong, Guo Hua" uniqKey="Fong G" first="Guo-Hua" last="Fong">Guo-Hua Fong</name><affiliation><nlm:aff id="aff10">Center for Vascular Biology, University of Connecticut, Farmington, CT 06030;</nlm:aff></affiliation></author><author><name sortKey="Ding, Hao" sort="Ding, Hao" uniqKey="Ding H" first="Hao" last="Ding">Hao Ding</name><affiliation><nlm:aff id="aff11">Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada MB R3E 3P5;</nlm:aff></affiliation></author><author><name sortKey="Greenberg, David A" sort="Greenberg, David A" uniqKey="Greenberg D" first="David A." last="Greenberg">David A. Greenberg</name><affiliation><nlm:aff wicri:cut="; and" id="aff12">Buck Institute for Age Research, Novato, CA 94945</nlm:aff></affiliation></author><author><name sortKey="Becker, Kevin G" sort="Becker, Kevin G" uniqKey="Becker K" first="Kevin G." last="Becker">Kevin G. Becker</name><affiliation><nlm:aff id="aff9">TRIAD Technology Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;</nlm:aff></affiliation></author><author><name sortKey="Herbert, Jean Marc" sort="Herbert, Jean Marc" uniqKey="Herbert J" first="Jean-Marc" last="Herbert">Jean-Marc Herbert</name><affiliation><nlm:aff id="aff8">Sanofi-Aventis Recherche, Cardiovascular-Thrombosis Research Department, 31036 Toulouse Cedex, France;</nlm:aff></affiliation></author><author><name sortKey="Nash, Andrew" sort="Nash, Andrew" uniqKey="Nash A" first="Andrew" last="Nash">Andrew Nash</name><affiliation><nlm:aff id="aff4">CSL Limited, Parkville, Victoria 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Yla Herttuala, Seppo" sort="Yla Herttuala, Seppo" uniqKey="Yla Herttuala S" first="Seppo" last="Yla-Herttuala">Seppo Yla-Herttuala</name><affiliation><nlm:aff id="aff5">Department of Biotechnology and Molecular Medicine, University of Kuopio, FIN-70211, Kuopio, Finland;</nlm:aff></affiliation></author><author><name sortKey="Cao, Yihai" sort="Cao, Yihai" uniqKey="Cao Y" first="Yihai" last="Cao">Yihai Cao</name><affiliation><nlm:aff id="aff13">Department of Microbiology, Karolinska Institute, 171 77 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Watts, Ryan J" sort="Watts, Ryan J" uniqKey="Watts R" first="Ryan J." last="Watts">Ryan J. Watts</name><affiliation><nlm:aff id="aff3">Neurodegeneration Labs, Protein Chemistry, Genentech, Inc. San Francisco, CA 94080;</nlm:aff></affiliation></author><author><name sortKey="Li, Xuri" sort="Li, Xuri" uniqKey="Li X" first="Xuri" last="Li">Xuri Li</name><affiliation><nlm:aff id="aff1">National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19369214</article-id><article-id pub-id-type="pmc">2669337</article-id><article-id pub-id-type="publisher-id">7578</article-id><article-id pub-id-type="doi">10.1073/pnas.0813061106</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Cell Biology</subject></subj-group></subj-group></article-categories><title-group><article-title>VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Fan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tang</surname><given-names>Zhongshu</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hou</surname><given-names>Xu</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lennartsson</surname><given-names>Johan</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Yang</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Koch</surname><given-names>Alexander W.</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Scotney</surname><given-names>Pierre</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Chunsik</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Arjunan</surname><given-names>Pachiappan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dong</surname><given-names>Lijin</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kumar</surname><given-names>Anil</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rissanen</surname><given-names>Tuomas T.</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Bin</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nagai</surname><given-names>Nobuo</given-names></name><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fons</surname><given-names>Pierre</given-names></name><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fariss</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Yongqing</given-names></name><xref ref-type="aff" rid="aff9"><sup>i</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wawrousek</surname><given-names>Eric</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tansey</surname><given-names>Ginger</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Raber</surname><given-names>James</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fong</surname><given-names>Guo-Hua</given-names></name><xref ref-type="aff" rid="aff10"><sup>j</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ding</surname><given-names>Hao</given-names></name><xref ref-type="aff" rid="aff11"><sup>k</sup></xref></contrib><contrib contrib-type="author"><name><surname>Greenberg</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="aff12"><sup>l</sup></xref></contrib><contrib contrib-type="author"><name><surname>Becker</surname><given-names>Kevin G.</given-names></name><xref ref-type="aff" rid="aff9"><sup>i</sup></xref></contrib><contrib contrib-type="author"><name><surname>Herbert</surname><given-names>Jean-Marc</given-names></name><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nash</surname><given-names>Andrew</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yla-Herttuala</surname><given-names>Seppo</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Yihai</given-names></name><xref ref-type="aff" rid="aff13"><sup>m</sup></xref></contrib><contrib contrib-type="author"><name><surname>Watts</surname><given-names>Ryan J.</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Xuri</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>a</sup>National Eye Institute, National Institutes of Health, Bethesda, MD 20892;</aff><aff id="aff2"><sup>b</sup>Ludwig Institute for Cancer Research, Uppsala University, SE-751 24 Uppsala, Sweden;</aff><aff id="aff3"><sup>c</sup>Neurodegeneration Labs, Protein Chemistry, Genentech, Inc. San Francisco, CA 94080;</aff><aff id="aff4"><sup>d</sup>CSL Limited, Parkville, Victoria 3052, Australia;</aff><aff id="aff5"><sup>e</sup>Department of Biotechnology and Molecular Medicine, University of Kuopio, FIN-70211, Kuopio, Finland;</aff><aff id="aff6"><sup>f</sup>Department of Radiology, Medical Imaging Centre of the Affiliated Hospital, Weifang Medical University, Weifang 261042, China;</aff><aff id="aff7"><sup>g</sup>Department of Physiology, Kinki University School of Medicine, Osaka 589-8511, Japan;</aff><aff id="aff8"><sup>h</sup>Sanofi-Aventis Recherche, Cardiovascular-Thrombosis Research Department, 31036 Toulouse Cedex, France;</aff><aff id="aff9"><sup>i</sup>TRIAD Technology Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;</aff><aff id="aff10"><sup>j</sup>Center for Vascular Biology, University of Connecticut, Farmington, CT 06030;</aff><aff id="aff11"><sup>k</sup>Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada MB R3E 3P5;</aff><aff id="aff12"><sup>l</sup>Buck Institute for Age Research, Novato, CA 94945; and</aff><aff id="aff13"><sup>m</sup>Department of Microbiology, Karolinska Institute, 171 77 Stockholm, Sweden</aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence should be addressed. E-mail: <email>lixur@nei.nih.gov</email></corresp><fn fn-type="edited-by"><p>Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved February 27, 2009</p></fn><fn fn-type="con"><p>Author contributions: X.L. designed research; F.Z., Z.T., X.H., J.L., Y.L., A.W.K., P.S., C.L., P.A., L.D., A.K., T.T.R., B.W., N.N., P.F., R.F., Y.Z., E.W., G.T., J.R., G.-H.F., H.D., D.A.G., K.G.B., J.-M.H., A.N., S.Y.-H., Y.C., and R.J.W. performed research; F.Z. and X.L. analyzed data; and F.Z. and X.L. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>14</day><month>4</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>6</day><month>4</month><year>2009</year></pub-date><volume>106</volume><issue>15</issue><fpage>6152</fpage><lpage>6157</lpage><history><date date-type="received"><day>29</day><month>12</month><year>2008</year></date></history><permissions></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq01509006152.pdf"></self-uri><abstract><p>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.</p></abstract><kwd-group><kwd>apoptosis</kwd><kwd>vascular survival</kwd><kwd>ocular neovascularization</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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