Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2
The establishment of functional and stable vascular networks is essential for angiogenic therapy. Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable...
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Veröffentlicht in: | Nature medicine 2003-05, Vol.9 (5), p.604-613 |
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description | The establishment of functional and stable vascular networks is essential for angiogenic therapy. Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable for more than a year even after depletion of angiogenic factors. In both rat and rabbit ischemic hind limb models, PDGF-BB and FGF-2 together markedly stimulated collateral arteriogenesis after ligation of the femoral artery, with a significant increase in vascularization and improvement in paw blood flow. A possible mechanism of angiogenic synergism between PDGF-BB and FGF-2 involves upregulation of the expression of PDGF receptor (PDGFR)-α and PDGFR-β by FGF-2 in newly formed blood vessels. Our data show that a specific combination of angiogenic factors establishes functional and stable vascular networks, and provides guidance for the ongoing clinical trials of angiogenic factors for the treatment of ischemic diseases. |
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Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable for more than a year even after depletion of angiogenic factors. In both rat and rabbit ischemic hind limb models, PDGF-BB and FGF-2 together markedly stimulated collateral arteriogenesis after ligation of the femoral artery, with a significant increase in vascularization and improvement in paw blood flow. A possible mechanism of angiogenic synergism between PDGF-BB and FGF-2 involves upregulation of the expression of PDGF receptor (PDGFR)-α and PDGFR-β by FGF-2 in newly formed blood vessels. Our data show that a specific combination of angiogenic factors establishes functional and stable vascular networks, and provides guidance for the ongoing clinical trials of angiogenic factors for the treatment of ischemic diseases.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/nm848</identifier><identifier>PMID: 12669032</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Blood Vessels - drug effects ; Cancer Research ; Collateral Circulation - drug effects ; Drug Synergism ; Fibroblast Growth Factor 2 - pharmacology ; Hindlimb - blood supply ; Infectious Diseases ; Ischemia - drug therapy ; Metabolic Diseases ; Mice ; Molecular Medicine ; Neovascularization, Physiologic - drug effects ; Neurosciences ; Platelet-Derived Growth Factor - pharmacology ; Proto-Oncogene Proteins c-sis ; Rabbits ; Rats ; Receptors, Platelet-Derived Growth Factor - biosynthesis ; Synergism</subject><ispartof>Nature medicine, 2003-05, Vol.9 (5), p.604-613</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c611t-5026f3f407f94955e6166672fa6c8641c4d4b3c8bb1175c0a9bb99ee1302c4c13</citedby><cites>FETCH-LOGICAL-c611t-5026f3f407f94955e6166672fa6c8641c4d4b3c8bb1175c0a9bb99ee1302c4c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nm848$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nm848$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12669032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1960196$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Renhai</creatorcontrib><creatorcontrib>Bråkenhielm, Ebba</creatorcontrib><creatorcontrib>Pawliuk, Robert</creatorcontrib><creatorcontrib>Wariaro, David</creatorcontrib><creatorcontrib>Post, Mark J.</creatorcontrib><creatorcontrib>Wahlberg, Eric</creatorcontrib><creatorcontrib>Leboulch, Philippe</creatorcontrib><creatorcontrib>Cao, Yihai</creatorcontrib><title>Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>The establishment of functional and stable vascular networks is essential for angiogenic therapy. Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable for more than a year even after depletion of angiogenic factors. In both rat and rabbit ischemic hind limb models, PDGF-BB and FGF-2 together markedly stimulated collateral arteriogenesis after ligation of the femoral artery, with a significant increase in vascularization and improvement in paw blood flow. A possible mechanism of angiogenic synergism between PDGF-BB and FGF-2 involves upregulation of the expression of PDGF receptor (PDGFR)-α and PDGFR-β by FGF-2 in newly formed blood vessels. Our data show that a specific combination of angiogenic factors establishes functional and stable vascular networks, and provides guidance for the ongoing clinical trials of angiogenic factors for the treatment of ischemic diseases.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood Vessels - drug effects</subject><subject>Cancer Research</subject><subject>Collateral Circulation - drug effects</subject><subject>Drug Synergism</subject><subject>Fibroblast Growth Factor 2 - pharmacology</subject><subject>Hindlimb - blood supply</subject><subject>Infectious Diseases</subject><subject>Ischemia - drug therapy</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Molecular Medicine</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Neurosciences</subject><subject>Platelet-Derived Growth Factor - pharmacology</subject><subject>Proto-Oncogene Proteins 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FGF-2</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>9</volume><issue>5</issue><spage>604</spage><epage>613</epage><pages>604-613</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>The establishment of functional and stable vascular networks is essential for angiogenic therapy. Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable for more than a year even after depletion of angiogenic factors. In both rat and rabbit ischemic hind limb models, PDGF-BB and FGF-2 together markedly stimulated collateral arteriogenesis after ligation of the femoral artery, with a significant increase in vascularization and improvement in paw blood flow. A possible mechanism of angiogenic synergism between PDGF-BB and FGF-2 involves upregulation of the expression of PDGF receptor (PDGFR)-α and PDGFR-β by FGF-2 in newly formed blood vessels. Our data show that a specific combination of angiogenic factors establishes functional and stable vascular networks, and provides guidance for the ongoing clinical trials of angiogenic factors for the treatment of ischemic diseases.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12669032</pmid><doi>10.1038/nm848</doi><tpages>10</tpages></addata></record> |
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subjects | Animals Biomedical and Life Sciences Biomedicine Blood Vessels - drug effects Cancer Research Collateral Circulation - drug effects Drug Synergism Fibroblast Growth Factor 2 - pharmacology Hindlimb - blood supply Infectious Diseases Ischemia - drug therapy Metabolic Diseases Mice Molecular Medicine Neovascularization, Physiologic - drug effects Neurosciences Platelet-Derived Growth Factor - pharmacology Proto-Oncogene Proteins c-sis Rabbits Rats Receptors, Platelet-Derived Growth Factor - biosynthesis Synergism |
title | Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2 |
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