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Liposomal prednisolone promotes macrophage lipotoxicity in experimental atherosclerosis.
van der Valk, Fleur M; Schulte, Dominik M; Meiler, Svenja; Tang, Jun; Zheng, Kang He; Van den Bossche, Jan; Seijkens, Tom; Laudes, Matthias; de Winther, Menno; Lutgens, Esther; Alaarg, Amr; Metselaar, Josbert M; Dallinga-Thie, Geesje M; Mulder, Willem J M; Stroes, Erik S G; Hamers, Anouk A J.
Afiliación
  • van der Valk FM; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: f.m.valkvander@amc.nl.
  • Schulte DM; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands; Department of Internal Medicine I, University Schleswig-Holstein, Arnold-Heller-Straße 3, Kiel, Germany. Electronic address: dominik.schulte@uksh.de.
  • Meiler S; Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: s.u.meiler@amc.uva.nl.
  • Tang J; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave, NY, USA. Electronic address: jun.tang.mssm@gmail.com.
  • Zheng KH; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: k.h.zheng@amc.uva.nl.
  • Van den Bossche J; Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: j.vandenbossche@amc.uva.nl.
  • Seijkens T; Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: t.t.seijkens@amc.uva.nl.
  • Laudes M; Department of Internal Medicine I, University Schleswig-Holstein, Arnold-Heller-Straße 3, Kiel, Germany. Electronic address: matthias.laudes@uk-sh.de.
  • de Winther M; Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: m.dewinther@amc.uva.nl.
  • Lutgens E; Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: e.lutgens@amc.uva.nl.
  • Alaarg A; Department of Biomaterials Science and Technology, Targeted Therapeutics section, MIRA Institute, University of Twente, Drienerlolaan 5, NB, Enschede, The Netherlands. Electronic address: A.M.S.A.Alaarg@uu.nl.
  • Metselaar JM; Department of Biomaterials Science and Technology, Targeted Therapeutics section, MIRA Institute, University of Twente, Drienerlolaan 5, NB, Enschede, The Netherlands. Electronic address: bart@enceladus.nl.
  • Dallinga-Thie GM; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: g.m.dallinga@amc.uva.nl.
  • Mulder WJ; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave, NY, USA. Electronic address: wjmmulder@gmail.com.
  • Stroes ES; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: e.s.stroes@amc.uva.nl.
  • Hamers AA; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: a.a.hamers@amc.uva.nl.
Nanomedicine ; 12(6): 1463-70, 2016 08.
Article en En | MEDLINE | ID: mdl-27015770
Atherosclerosis is a lipid-driven inflammatory disease, for which nanomedicinal interventions are under evaluation. Previously, we showed that liposomal nanoparticles loaded with prednisolone (LN-PLP) accumulated in plaque macrophages, however, induced proatherogenic effects in patients. Here, we confirmed in low-density lipoprotein receptor knockout (LDLr(-/-)) mice that LN-PLP accumulates in plaque macrophages. Next, we found that LN-PLP infusions at 10mg/kg for 2weeks enhanced monocyte recruitment to plaques. In follow up, after 6weeks of LN-PLP exposure we observed (i) increased macrophage content, (ii) more advanced plaque stages, and (iii) larger necrotic core sizes. Finally, in vitro studies showed that macrophages become lipotoxic after LN-PLP exposure, exemplified by enhanced lipid loading, ER stress and apoptosis. These findings indicate that liposomal prednisolone may paradoxically accelerate atherosclerosis by promoting macrophage lipotoxicity. Hence, future (nanomedicinal) drug development studies are challenged by the multifactorial nature of atherosclerotic inflammation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prednisolona / Aterosclerosis Límite: Animals / Humans Idioma: En Revista: Nanomedicine Asunto de la revista: BIOTECNOLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prednisolona / Aterosclerosis Límite: Animals / Humans Idioma: En Revista: Nanomedicine Asunto de la revista: BIOTECNOLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos