Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA789533 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:ApoE-/- and Bl6 mice were fed normal chow of high fat diet. CD11c+ cells were isolated from mouse spleens. and mRNA expression was quantified using gene arrays.
2021-12-18 | GSE191044 | GEO
Project description: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.
| S-EPMC8749187 | biostudies-literature
Project description:Atherosclerosis is a chronic disease characterized by both dysregulated lipid metabolism and a sustained inflammatory reaction. To study exuberant inflammation as the main trigger of atherosclerosis, we established a novel in vivo approach to induce predominantly “immune-triggered atherosclerosis” for early atherogenesis independent of lipid dysregulation. Bone marrow from CD11c.DTR-GFP mice, which express the receptor for diphtheria toxin (DT) under control of the CD11c promoter, was transplanted into female C57BL/6 mice, and long-term depletion of antigen-presenting CD11c+ cells following DT administration was achieved without affecting lipid homeostasis. These mice exhibited enhanced atherosclerosis (~300%) in comparison to mice without CD11c+ cell depletion. Interestingly, we observed an altered immune cell composition within the aortic wall, including a decrease in tolerogenic DCs, a shift towards inflammatory Ly6G+/Ly6C+ monocytes and increased CD25+/FoxP3+ T cells, whereby the intracellular cytokine profile showed an increase of TNF- α, INF-γ and IL-17. We furthermore detected a pronounced systemic inflammatory response with increased levels of TNF-α, INFγ, IL-17 and IL-1β. Thus, CD11c+ cells are the decisive cellular brake preventing an exuberant inflammatory response in early atherogenesis. Here, we describe a novel tool for studying the role of immune cells and associated mechanisms in atherosclerosis in mice with intact lipid metabolism.
2025-08-31 | GSE275805 | GEO
Project description:Atherosclerosis is a chronic disease characterized by both dysregulated lipid metabolism and a sustained inflammatory reaction. To study exuberant inflammation as the main trigger of atherosclerosis, we established a novel in vivo approach to induce predominantly “immune-triggered atherosclerosis” for early atherogenesis independent of lipid dysregulation. Bone marrow from CD11c.DTR-GFP mice, which express the receptor for diphtheria toxin (DT) under control of the CD11c promoter, was transplanted into female C57BL/6 mice, and long-term depletion of antigen-presenting CD11c+ cells following DT administration was achieved without affecting lipid homeostasis. These mice exhibited enhanced atherosclerosis (~300%) in comparison to mice without CD11c+ cell depletion. Interestingly, we observed an altered immune cell composition within the aortic wall, including a decrease in tolerogenic DCs, a shift towards inflammatory Ly6G+/Ly6C+ monocytes and increased CD25+/FoxP3+ T cells, whereby the intracellular cytokine profile showed an increase of TNF- α, INF-γ and IL-17. We furthermore detected a pronounced systemic inflammatory response with increased levels of TNF-α, INFγ, IL-17 and IL-1β. Thus, CD11c+ cells are the decisive cellular brake preventing an exuberant inflammatory response in early atherogenesis. Here, we describe a novel tool for studying the role of immune cells and associated mechanisms in atherosclerosis in mice with intact lipid metabolism.
2025-08-31 | GSE275865 | GEO
Project description:Lack of tolerogenic CD11c+ cells drives early atherosclerosis [RNA-seq]
| PRJNA1152993 | ENA
Project description:Lack of tolerogenic CD11c+ cells drives early atherosclerosis [scRNA-seq]
| PRJNA1153396 | ENA
Project description:Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels with limited preventive and treatment options currently available. Previous experiments have demonstrated the atheroprotective potential of collagen 6 subtype alpha6 (COL6A6) in apolipoprotein E-deficient (ApoE-/-) mice with hyperlipidemia. However, the mechanism underlying the anti-atherosclerotic effects of COL6A6 remains elusive. This knowledge gap was addressed in the present study by immunizing ApoE-/- mice with the Pep_A6 vaccine, comprising a COL6A6 peptide-KLH (keyhole limpet hemocyanin) conjugate and aluminum (Alum) hydroxide adjuvant, and conducting a series of experiments. Our objective was to investigate the efficacy of the Pep_A6 vaccine, focusing on immune responses and lipid metabolism. Our finding showed that the Pep_A6 vaccine represents a novel approach to combat atherosclerosis by inducing a large increase in Treg cells, the generation of antigen-specific antibodies and regulating lipid metabolism.
2024-10-02 | GSE245813 | GEO
Project description:Ubiquitination of hepatic APOC3 by GM47544 prevents hypertriglyceridemia and ameliorates atherosclerosis
| PRJNA974253 | ENA
Project description:Dendritic cells (DCs) are essential for priming of immune responses. Although immune mechanisms are known to control the pathogenesis of atherosclerosis, the role of DCs remains elusive. Here we show that Ccl17 expressing mature, myeloid DCs accumulate within atherosclerotic lesions. Deletion of Ccl17 in apolipoprotein E-deficient (Apoe-/-) mice reduces the development and progression of atherosclerosis in several disease models. While Ccl17 expression by DCs dampened antigen-specific T cell proliferation, it is required for efficient polarization of T helper type 1 (Th1) and Th17 as reflected by a preponderance of Th2 cytokines in Ccl17-/- Apoe-/- mice. In line with these findings, only transfer of T cells from Apoe-/-, but not from Ccl17-/- Apoe-/- precipitated atherosclerosis in T cell depleted Apoe-/- recipients. These findings identify Ccl17+ DCs as central immune regulators in atherosclerosis and Ccl17 as a potential target in the treatment of this disease. There were two samples analyzed with no replicates included. The two samples should be compared with each other.
2011-11-01 | E-GEOD-13642 | biostudies-arrayexpress
Project description:The project was designed to identify genes with an altered expression in macrophages from subjects with atherosclerosis compared to macrophages from control subjects. Experiment Overall Design: We used monocyte-derived macrophages from peripheral blood cultured in the absence or presence of oxidized LDL, baseline macrophages or foam cells. The macrophages were obtained from 15 subjects with subclinical atherosclerosis and a family history of CHD. Macrophages from 15 age and sexmatched subjects with no atherosclerosis and no family history of CHD were used as control.
2008-06-17 | E-GEOD-9874 | biostudies-arrayexpress