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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2002-9-6
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pubmed:abstractText |
Identification of factors that may stimulate ischemia-induced neovascularization without increasing atherosclerotic plaque progression is of major therapeutic importance. We hypothesized that interleukin-18 binding protein (IL-18BP), a major antiinflammatory protein with plaque-stabilizing activities, may affect the neovascularization in mice ischemic hindlimb. Ischemia was produced by artery femoral occlusion in mice that were subjected to in vivo intramuscular electrotransfer of either an empty plasmid or a murine IL-18BP plasmid. Angiographic score, capillary density (CD31 staining), and laser Doppler perfusion data at day 28 showed significant improvement in ischemic/nonischemic leg ratio by respectively 1.6-, 1.4-, and 1.5-fold in IL-18BP-treated mice compared with controls (P<0.01). This was associated with a significant 2-fold increase in both vascular endothelial growth factor (VEGF) and phospho-Akt protein content in the ischemic hindlimb of IL-18BP-treated mice (P<0.05). Similar results were obtained in IL-18-deficient mice. Because bone marrow-derived endothelial progenitor cells (BM-EPCs) are involved in postnatal vasculogenesis, EPCs were isolated and cultivated from bone marrow mononuclear cells. IL-18BP treatment led to a significant 1.8-fold increase in the percentage of BM-EPCs characterized as cells positive for both AcLDL-Dil and von Willebrand factor (P<0.001). In conclusion, IL-18BP stimulates ischemia-induced neovascularization in association with an activation of VEGF/Akt signaling and an increase in BM-EPCs mobilization and differentiation. Our findings strongly suggest a major antiangiogenic role of endogenous IL-18 in postischemic injury.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/NOS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Nos3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/interleukin-18 binding protein
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1524-4571
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pubmed:author |
pubmed-author:AkiraShizuoS,
pubmed-author:BarateauVéroniqueV,
pubmed-author:ChvatchkoYolandeY,
pubmed-author:ClergueMichelM,
pubmed-author:CorbazAnneA,
pubmed-author:DuriezMichelineM,
pubmed-author:LévyBernard IBI,
pubmed-author:Le Ricousse-RoussanneSophieS,
pubmed-author:Lecomte-RacletLaurenceL,
pubmed-author:MallatZiadZ,
pubmed-author:SilvestreJean-SébastienJS,
pubmed-author:TedguiAlainA,
pubmed-author:TobelemGérardG
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
91
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
441-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12215494-Angiography,
pubmed-meshheading:12215494-Animals,
pubmed-meshheading:12215494-Bone Marrow Cells,
pubmed-meshheading:12215494-Cell Line,
pubmed-meshheading:12215494-Endothelial Growth Factors,
pubmed-meshheading:12215494-Endothelium, Vascular,
pubmed-meshheading:12215494-Glycoproteins,
pubmed-meshheading:12215494-Hindlimb,
pubmed-meshheading:12215494-Humans,
pubmed-meshheading:12215494-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12215494-Interleukin-18,
pubmed-meshheading:12215494-Ischemia,
pubmed-meshheading:12215494-Laser-Doppler Flowmetry,
pubmed-meshheading:12215494-Lymphokines,
pubmed-meshheading:12215494-Male,
pubmed-meshheading:12215494-Mice,
pubmed-meshheading:12215494-Mice, Inbred C57BL,
pubmed-meshheading:12215494-Mice, Knockout,
pubmed-meshheading:12215494-Neovascularization, Pathologic,
pubmed-meshheading:12215494-Neovascularization, Physiologic,
pubmed-meshheading:12215494-Nitric Oxide Synthase,
pubmed-meshheading:12215494-Nitric Oxide Synthase Type II,
pubmed-meshheading:12215494-Nitric Oxide Synthase Type III,
pubmed-meshheading:12215494-Phosphorylation,
pubmed-meshheading:12215494-Plasmids,
pubmed-meshheading:12215494-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12215494-Proto-Oncogene Proteins,
pubmed-meshheading:12215494-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12215494-Vascular Endothelial Growth Factor A,
pubmed-meshheading:12215494-Vascular Endothelial Growth Factors
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pubmed:year |
2002
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pubmed:articleTitle |
Interleukin-18/interleukin-18 binding protein signaling modulates ischemia-induced neovascularization in mice hindlimb.
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pubmed:affiliation |
INSERM U541, Hôpital Lariboisière, IFR Circulation-Paris 7, Université Paris 7, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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