Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis
Summary: Atherosclerosis is studied in models with dysfunctional lipid homeostasis—predominantly the ApoE−/− mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c+ cells were enriched in aortae of ApoE−/− mice. System...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221016473 |
| _version_ | 1818975901973479424 |
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| author | Manuela Sauter Reinhard J. Sauter Henry Nording Chaolan Lin Marcus Olbrich Stella Autenrieth Christian Gleissner Martin Thunemann Nadia Otero Esther Lutgens Zouhair Aherrahrou Dennis Wolf Lars Zender Sven Meuth Robert Feil Harald F. Langer |
| author_facet | Manuela Sauter Reinhard J. Sauter Henry Nording Chaolan Lin Marcus Olbrich Stella Autenrieth Christian Gleissner Martin Thunemann Nadia Otero Esther Lutgens Zouhair Aherrahrou Dennis Wolf Lars Zender Sven Meuth Robert Feil Harald F. Langer |
| author_sort | Manuela Sauter |
| collection | DOAJ |
| description | Summary: Atherosclerosis is studied in models with dysfunctional lipid homeostasis—predominantly the ApoE−/− mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c+ cells were enriched in aortae of ApoE−/− mice. Systemic long-term depletion of CD11c+ cells in ApoE−/− mice resulted in significantly increased plaque formation associated with reduced serum ApoE levels. In CD11ccre+ApoEfl/fl and Albumincre+ApoEfl/fl mice, we could show that ≈70% of ApoE is liver-derived and ≈25% originates from CD11c+ cells associated with significantly increased atherosclerotic plaque burden in both strains. Exposure to acLDL promoted cholesterol efflux from CD11c+ cells and cell-specific deletion of ApoE resulted in increased inflammation reflected by increased IL-1β serum levels. Our results determined for the first time the level of ApoE originating from CD11c+ cells and demonstrated that CD11c+ cells ameliorate atherosclerosis by the secretion of ApoE. |
| first_indexed | 2024-12-20T16:03:19Z |
| format | Article |
| id | doaj.art-8372ba129da94ea188c19d26d88c8880 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-20T16:03:19Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8372ba129da94ea188c19d26d88c88802022-12-21T19:34:13ZengElsevieriScience2589-00422022-01-01251103677Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosisManuela Sauter0Reinhard J. Sauter1Henry Nording2Chaolan Lin3Marcus Olbrich4Stella Autenrieth5Christian Gleissner6Martin Thunemann7Nadia Otero8Esther Lutgens9Zouhair Aherrahrou10Dennis Wolf11Lars Zender12Sven Meuth13Robert Feil14Harald F. Langer15Department of Cardiology, University Hospital, Medical Clinic II, University Heart Center Luebeck, Ratzeburger Allee 160, 23538 Luebeck, GermanyDepartment of Cardiology, University Hospital, Medical Clinic II, University Heart Center Luebeck, Ratzeburger Allee 160, 23538 Luebeck, GermanyDepartment of Cardiology, University Hospital, Medical Clinic II, University Heart Center Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany; DZHK (German Research Centre for Cardiovascular Research), Partner Site Hamburg/Luebeck/Kiel, 23562 Luebeck, GermanyDepartment of Cardiology, University Hospital, Medical Clinic II, University Heart Center Luebeck, Ratzeburger Allee 160, 23538 Luebeck, GermanyUniversity Hospital, Department of Cardiology, Eberhard Karls University Tuebingen, 72076 Tuebingen, GermanyUniversity Hospital, Department of Hematology and Oncology, Eberhard Karls University Tuebingen, 72076 Tuebingen, GermanyUniversity Hospital, Department of Cardiology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USAPhilipps University Marburg, Faculty of Medicine, 35043 Marburg, GermanyUniversity Hospital Munich, Institute for Prophylaxis and Epidemiology of Circulatory Diseases, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyUniversity of Luebeck, Institute of Cardiogenetics, 23538 Luebeck, GermanyUniversity Hospital, Department of Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, 79106 Freiburg, GermanyDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany; DFG Cluster of Excellence 2180 'Image-guided and Functional Instructed Tumor Therapy' (IFIT), University of Tuebingen, 72076 Tuebingen, Germany; German Cancer Research Consortium (DKTK), Partner Site Tübingen, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyUniversity Hospital, Department of Neurology, University of Duesseldorf, 40225 Duesseldorf, GermanyInterfaculty Institute of Biochemistry, University of Tuebingen, 72076 Tuebingen, GermanyDepartment of Cardiology, University Hospital, Medical Clinic II, University Heart Center Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany; Corresponding authorSummary: Atherosclerosis is studied in models with dysfunctional lipid homeostasis—predominantly the ApoE−/− mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c+ cells were enriched in aortae of ApoE−/− mice. Systemic long-term depletion of CD11c+ cells in ApoE−/− mice resulted in significantly increased plaque formation associated with reduced serum ApoE levels. In CD11ccre+ApoEfl/fl and Albumincre+ApoEfl/fl mice, we could show that ≈70% of ApoE is liver-derived and ≈25% originates from CD11c+ cells associated with significantly increased atherosclerotic plaque burden in both strains. Exposure to acLDL promoted cholesterol efflux from CD11c+ cells and cell-specific deletion of ApoE resulted in increased inflammation reflected by increased IL-1β serum levels. Our results determined for the first time the level of ApoE originating from CD11c+ cells and demonstrated that CD11c+ cells ameliorate atherosclerosis by the secretion of ApoE.http://www.sciencedirect.com/science/article/pii/S2589004221016473Biological sciencesMolecular biologyImmune responseComponents of the immune system |
| spellingShingle | Manuela Sauter Reinhard J. Sauter Henry Nording Chaolan Lin Marcus Olbrich Stella Autenrieth Christian Gleissner Martin Thunemann Nadia Otero Esther Lutgens Zouhair Aherrahrou Dennis Wolf Lars Zender Sven Meuth Robert Feil Harald F. Langer Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis iScience Biological sciences Molecular biology Immune response Components of the immune system |
| title | Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis |
| title_full | Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis |
| title_fullStr | Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis |
| title_full_unstemmed | Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis |
| title_short | Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis |
| title_sort | apolipoprotein e derived from cd11c cells ameliorates atherosclerosis |
| topic | Biological sciences Molecular biology Immune response Components of the immune system |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221016473 |
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