A new synthetic FGF receptor antagonist inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice
The role of fibroblast growth factors (FGFs) in the development of vascular diseases remains incompletely understood. The objective of this study was to examine the effects of a new small-molecule multi-FGF receptor blocker with allosteric properties, SSR128129E, on neointimal proliferation after a...
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| creator | Dol-Gleizes, Frédérique Delesque-Touchard, Nathalie Marès, Anne-Marie Nestor, Anne-Laure Schaeffer, Paul Bono, Françoise |
| description | The role of fibroblast growth factors (FGFs) in the development of vascular diseases remains incompletely understood. The objective of this study was to examine the effects of a new small-molecule multi-FGF receptor blocker with allosteric properties, SSR128129E, on neointimal proliferation after a vein graft procedure in mice and on the development of atherosclerosis in atherosclerosis-prone apolipoprotein E (apoE)-deficient mice.
Vein grafts were performed in 3 month-old male C57BL6 mice. Segments of the vena cava were interposed at the level of the carotid artery. In SSR128129E (50 mg/kg/d)-treated animals, a dramatic decrease in neointimal proliferation was observed 2 and 8 weeks after the graft (72.5%, p |
| doi_str_mv | 10.1371/journal.pone.0080027 |
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Vein grafts were performed in 3 month-old male C57BL6 mice. Segments of the vena cava were interposed at the level of the carotid artery. In SSR128129E (50 mg/kg/d)-treated animals, a dramatic decrease in neointimal proliferation was observed 2 and 8 weeks after the graft (72.5%, p<0.01, and 47.8%, p<0.05, respectively). Four-week old male apoE-deficient mice were treated with SSR128129E (50 mg/kg/d) for 3 and 5 months in comparison with a control group. SSR128129E treatment resulted in a reduction of lesion size in the aortic sinus (16.4% (ns) at 3 months and 42.9% (p<0.01) at 5 months, without any change in serum lipids. SSR128129 significantly reduced FGFR2 mRNA levels in the aortic sinus (p<0.05, n=5-6), but did not affect the mRNA expression levels of other FGF receptors or ligands.
These studies indicate that FGFs have an important role in the development of vascular diseases like atherosclerosis and graft arteriosclerosis. These data suggest that inhibition of FGF receptors by compounds like SSR128129E might be useful as a new therapeutic approach for these vascular pathologies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0080027</identifier><identifier>PMID: 24224032</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Allosteric properties ; Analysis ; Angiogenesis ; Animals ; Aorta ; Apolipoprotein E ; Apolipoproteins ; Apolipoproteins E - deficiency ; Apolipoproteins E - genetics ; Apoptosis ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - drug therapy ; Atherosclerosis - metabolism ; Atherosclerosis - surgery ; Blood circulation disorders ; Blood lipids ; Carotid arteries ; Carotid artery ; Cell growth ; Chemokines ; Fibroblast growth factor receptor 2 ; Fibroblast growth factors ; Fibroblasts ; Gene expression ; Grafting ; Grafts ; Growth factors ; Kinases ; Lipids ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors ; Receptors, Fibroblast Growth Factor - antagonists & inhibitors ; Receptors, Fibroblast Growth Factor - metabolism ; RNA ; Rodents ; Serum lipids ; Sinus ; Smooth muscle ; Vascular diseases ; Veins & arteries ; Veins - surgery ; Veins - transplantation</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e80027-e80027</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Dol-Gleizes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Dol-Gleizes et al 2013 Dol-Gleizes et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-90206c4ff8f15be0b837d170a7514511847c6deb08ec404cd201387e3473cd543</citedby><cites>FETCH-LOGICAL-c692t-90206c4ff8f15be0b837d170a7514511847c6deb08ec404cd201387e3473cd543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817113/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817113/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24224032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dol-Gleizes, Frédérique</creatorcontrib><creatorcontrib>Delesque-Touchard, Nathalie</creatorcontrib><creatorcontrib>Marès, Anne-Marie</creatorcontrib><creatorcontrib>Nestor, Anne-Laure</creatorcontrib><creatorcontrib>Schaeffer, Paul</creatorcontrib><creatorcontrib>Bono, Françoise</creatorcontrib><title>A new synthetic FGF receptor antagonist inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The role of fibroblast growth factors (FGFs) in the development of vascular diseases remains incompletely understood. The objective of this study was to examine the effects of a new small-molecule multi-FGF receptor blocker with allosteric properties, SSR128129E, on neointimal proliferation after a vein graft procedure in mice and on the development of atherosclerosis in atherosclerosis-prone apolipoprotein E (apoE)-deficient mice.
Vein grafts were performed in 3 month-old male C57BL6 mice. Segments of the vena cava were interposed at the level of the carotid artery. In SSR128129E (50 mg/kg/d)-treated animals, a dramatic decrease in neointimal proliferation was observed 2 and 8 weeks after the graft (72.5%, p<0.01, and 47.8%, p<0.05, respectively). Four-week old male apoE-deficient mice were treated with SSR128129E (50 mg/kg/d) for 3 and 5 months in comparison with a control group. SSR128129E treatment resulted in a reduction of lesion size in the aortic sinus (16.4% (ns) at 3 months and 42.9% (p<0.01) at 5 months, without any change in serum lipids. SSR128129 significantly reduced FGFR2 mRNA levels in the aortic sinus (p<0.05, n=5-6), but did not affect the mRNA expression levels of other FGF receptors or ligands.
These studies indicate that FGFs have an important role in the development of vascular diseases like atherosclerosis and graft arteriosclerosis. These data suggest that inhibition of FGF receptors by compounds like SSR128129E might be useful as a new therapeutic approach for these vascular pathologies.</description><subject>Allosteric properties</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Aorta</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins</subject><subject>Apolipoproteins E - deficiency</subject><subject>Apolipoproteins E - genetics</subject><subject>Apoptosis</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - drug therapy</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - surgery</subject><subject>Blood circulation disorders</subject><subject>Blood lipids</subject><subject>Carotid arteries</subject><subject>Carotid artery</subject><subject>Cell growth</subject><subject>Chemokines</subject><subject>Fibroblast growth factor receptor 2</subject><subject>Fibroblast growth factors</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Grafting</subject><subject>Grafts</subject><subject>Growth factors</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Receptors</subject><subject>Receptors, Fibroblast Growth Factor - antagonists & inhibitors</subject><subject>Receptors, Fibroblast Growth Factor - metabolism</subject><subject>RNA</subject><subject>Rodents</subject><subject>Serum lipids</subject><subject>Sinus</subject><subject>Smooth muscle</subject><subject>Vascular diseases</subject><subject>Veins & arteries</subject><subject>Veins - surgery</subject><subject>Veins - transplantation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk89u1DAQxiMEoqXwBggiISE47GLHTuJckFZVt6xUqRL_rpZjT7KusnZqO4W-Bw-Mw6bVpuoB5ZBk_Ps-z4w9SfIaoyUmJf50ZQdnRLfsrYElQgyhrHySHOOKZIsiQ-TpwfdR8sL7K4RyworieXKU0SyjiGTHyZ9VauBX6m9N2ELQMl2fr1MHEvpgXSpMEK012odUm62udfCpcAGctl524KzXPq6kIt3ZwUN6A_GndaIJMaCgiwYqFdHZPeB72-ne9s6GUXG2UNBoqcFEnZbwMnnWiM7Dq-l9kvxYn30__bK4uDzfnK4uFrKosrCoUIYKSZuGNTivAdWMlAqXSJQ5pjnGjJayUFAjBpIiKlWGMGElEFoSqXJKTpK3e9--s55PDfUcU8ooLvJiJDZ7QllxxXund8Ldcis0_xewruWxHzrWxvOiAdywSsq8jjkVVVVXFEGNi1qVSpDo9Xnabah3oGSs1oluZjpfMXrLW3vDCcMlxqPBh8nA2esBfOA77SV0nTAQ2x_zzlmO4hGPeb97gD5e3US1IhagTWPjvnI05StaMprlVVVFavkIFR8F8bDi7Wt0jM8EH2eCyAT4HVoxeM83377-P3v5c86-P2C3ILqw9bYbgrbGz0G6B2W8cd5Bc99kjPg4PHfd4OPw8Gl4ouzN4QHdi-6mhfwF1xcW7A</recordid><startdate>20131104</startdate><enddate>20131104</enddate><creator>Dol-Gleizes, Frédérique</creator><creator>Delesque-Touchard, Nathalie</creator><creator>Marès, Anne-Marie</creator><creator>Nestor, Anne-Laure</creator><creator>Schaeffer, Paul</creator><creator>Bono, Françoise</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131104</creationdate><title>A new synthetic FGF receptor antagonist inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice</title><author>Dol-Gleizes, Frédérique ; Delesque-Touchard, Nathalie ; Marès, Anne-Marie ; Nestor, Anne-Laure ; Schaeffer, Paul ; Bono, Françoise</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-90206c4ff8f15be0b837d170a7514511847c6deb08ec404cd201387e3473cd543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Allosteric properties</topic><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Aorta</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins</topic><topic>Apolipoproteins E - deficiency</topic><topic>Apolipoproteins E - genetics</topic><topic>Apoptosis</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - drug therapy</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - surgery</topic><topic>Blood circulation disorders</topic><topic>Blood lipids</topic><topic>Carotid arteries</topic><topic>Carotid artery</topic><topic>Cell growth</topic><topic>Chemokines</topic><topic>Fibroblast growth factor receptor 2</topic><topic>Fibroblast growth factors</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Grafting</topic><topic>Grafts</topic><topic>Growth factors</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Receptors</topic><topic>Receptors, Fibroblast Growth Factor - antagonists & inhibitors</topic><topic>Receptors, Fibroblast Growth Factor - metabolism</topic><topic>RNA</topic><topic>Rodents</topic><topic>Serum lipids</topic><topic>Sinus</topic><topic>Smooth muscle</topic><topic>Vascular diseases</topic><topic>Veins & arteries</topic><topic>Veins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dol-Gleizes, Frédérique</au><au>Delesque-Touchard, Nathalie</au><au>Marès, Anne-Marie</au><au>Nestor, Anne-Laure</au><au>Schaeffer, Paul</au><au>Bono, Françoise</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new synthetic FGF receptor antagonist inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-04</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e80027</spage><epage>e80027</epage><pages>e80027-e80027</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The role of fibroblast growth factors (FGFs) in the development of vascular diseases remains incompletely understood. The objective of this study was to examine the effects of a new small-molecule multi-FGF receptor blocker with allosteric properties, SSR128129E, on neointimal proliferation after a vein graft procedure in mice and on the development of atherosclerosis in atherosclerosis-prone apolipoprotein E (apoE)-deficient mice.
Vein grafts were performed in 3 month-old male C57BL6 mice. Segments of the vena cava were interposed at the level of the carotid artery. In SSR128129E (50 mg/kg/d)-treated animals, a dramatic decrease in neointimal proliferation was observed 2 and 8 weeks after the graft (72.5%, p<0.01, and 47.8%, p<0.05, respectively). Four-week old male apoE-deficient mice were treated with SSR128129E (50 mg/kg/d) for 3 and 5 months in comparison with a control group. SSR128129E treatment resulted in a reduction of lesion size in the aortic sinus (16.4% (ns) at 3 months and 42.9% (p<0.01) at 5 months, without any change in serum lipids. SSR128129 significantly reduced FGFR2 mRNA levels in the aortic sinus (p<0.05, n=5-6), but did not affect the mRNA expression levels of other FGF receptors or ligands.
These studies indicate that FGFs have an important role in the development of vascular diseases like atherosclerosis and graft arteriosclerosis. These data suggest that inhibition of FGF receptors by compounds like SSR128129E might be useful as a new therapeutic approach for these vascular pathologies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24224032</pmid><doi>10.1371/journal.pone.0080027</doi><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Allosteric properties Analysis Angiogenesis Animals Aorta Apolipoprotein E Apolipoproteins Apolipoproteins E - deficiency Apolipoproteins E - genetics Apoptosis Arteriosclerosis Atherosclerosis Atherosclerosis - drug therapy Atherosclerosis - metabolism Atherosclerosis - surgery Blood circulation disorders Blood lipids Carotid arteries Carotid artery Cell growth Chemokines Fibroblast growth factor receptor 2 Fibroblast growth factors Fibroblasts Gene expression Grafting Grafts Growth factors Kinases Lipids Male Mice Mice, Inbred C57BL Mice, Knockout Receptors Receptors, Fibroblast Growth Factor - antagonists & inhibitors Receptors, Fibroblast Growth Factor - metabolism RNA Rodents Serum lipids Sinus Smooth muscle Vascular diseases Veins & arteries Veins - surgery Veins - transplantation |
| title | A new synthetic FGF receptor antagonist inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T05%3A01%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20new%20synthetic%20FGF%20receptor%20antagonist%20inhibits%20arteriosclerosis%20in%20a%20mouse%20vein%20graft%20model%20and%20atherosclerosis%20in%20apolipoprotein%20E-deficient%20mice&rft.jtitle=PloS%20one&rft.au=Dol-Gleizes,%20Fr%C3%A9d%C3%A9rique&rft.date=2013-11-04&rft.volume=8&rft.issue=11&rft.spage=e80027&rft.epage=e80027&rft.pages=e80027-e80027&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0080027&rft_dat=%3Cgale_plos_%3EA478425999%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1448416564&rft_id=info:pmid/24224032&rft_galeid=A478425999&rft_doaj_id=oai_doaj_org_article_56fe1f89cc5b4ff699b940eb16bd7da3&rfr_iscdi=true |