Selective EGFR (Epidermal Growth Factor Receptor) Deletion in Myeloid Cells Limits Atherosclerosis—Brief Report
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- Lynda Zeboudj
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Andréas Giraud
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Lea Guyonnet
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Yujiao Zhang
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Ludivine Laurans
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Bruno Esposito
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Jose Vilar
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Anna Chipont
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Nikolina Papac-Milicevic
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Christoph J. Binder
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Alain Tedgui
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Ziad Mallat
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Pierre-Louis Tharaux
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
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- Hafid Ait-Oufella
- From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation...
Abstract
<jats:sec> <jats:title>Objective—</jats:title> <jats:p>To determine the consequences of specific inhibition of EGFR (epidermal growth factor receptor) in myeloid cells in atherosclerosis development.</jats:p> </jats:sec> <jats:sec> <jats:title>Approach and Results—</jats:title> <jats:p> Atherosclerotic lesion size was significantly reduced in irradiated <jats:italic>Ldlr</jats:italic> <jats:sup>−/−</jats:sup> mice reconstituted with <jats:italic>LysM</jats:italic> <jats:sup> <jats:italic>Cre+</jats:italic> </jats:sup> <jats:italic>Egfr</jats:italic> <jats:sup> <jats:italic>lox/lox</jats:italic> </jats:sup> bone marrow, compared with chimeric <jats:italic>Ldlr</jats:italic> <jats:sup>−/−</jats:sup> mice reconstituted with <jats:italic>LysM</jats:italic> <jats:sup> <jats:italic>Cre−</jats:italic> </jats:sup> <jats:italic>Egfr</jats:italic> <jats:sup> <jats:italic>lox/lox</jats:italic> </jats:sup> bone marrow, after 4 (−43%; <jats:italic>P</jats:italic> <0.05), 7 (−34%; <jats:italic>P</jats:italic> <0.05), and 12 weeks (−54%; <jats:italic>P</jats:italic> <0.001) of high-fat diet. Reduction of lesion size was associated with marked reduction in macrophage accumulation and necrotic core size. Specific deletion of <jats:italic>Egfr</jats:italic> in myeloid cells reduced TNF-α (tumor necrosis factor-α) and IL (interleukin)-6 production by stimulated macrophages but had no effect on IL-10 and IL-12p70 secretion. Finally, we found that myeloid deletion of <jats:italic>Egfr</jats:italic> limited cytoskeletal rearrangements and also lipid uptake by macrophages through a downregulation of the scavenger receptor CD36 (cluster of differentiation 36). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p> Gene deletion of <jats:italic>Egfr</jats:italic> in myeloid cells limits IL-6 and TNF-α production, lipid uptake, and consecutively reduces atherosclerosis development. </jats:p> </jats:sec>
Journal
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- Arteriosclerosis, Thrombosis, and Vascular Biology
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Arteriosclerosis, Thrombosis, and Vascular Biology 38 (1), 114-119, 2018-01
Ovid Technologies (Wolters Kluwer Health)
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Details 詳細情報について
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- CRID
- 1360282588967117696
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- ISSN
- 15244636
- 10795642
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- Data Source
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- Crossref