Apolipoprotein E derived from CD11c(+) cells ameliorates atherosclerosis

Sauter, Manuela; Sauter, Reinhard J.; Nording, Henry; Lin, Chaolan; Olbrich, Marcus; Autenrieth, Stella; Gleissner, Christian; Thunemann, Martin; Otero, Nadia; Lutgens, Esther; Aherrahrou, Zouhair; Wolf, Dennis; Zender, Lars; Meuth, Sven; Feil, Robert und Langer, Harald F. (2022): Apolipoprotein E derived from CD11c(+) cells ameliorates atherosclerosis. In: iScience, Bd. 25, Nr. 1, 103677

Abstract

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-termdepletion of CD11c(+) cells in ApoE(-/-) mice resulted in significantly increased plaque formation associated with reduced serum ApoE levels. In CD11c(cre+)ApoE(fl/fl) and Albumin(cre)+ApoE(fl/fl )mice, we could show that approximate to 70% of ApoE is liver-derived and approximate to 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-1 beta 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 374031971