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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...
  • 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...

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<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>

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