Macrophage extracellular traps originated from the vascular smooth muscle cells play key roles in atherosclerosis progression.
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE197075 | GEO | 2022/11/04
REPOSITORIES: GEO
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Project description:Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC transdifferentiation into macrophage-like SMCs. Furthermore, during transdifferentiation, the SMCs' expression of PADI4 upregulating and SMC generated extracellular trap, a web-like structure, which plays key role in the development of atherosclerosis plaque. To reveal the function of SMC's generating ETs during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of mouse atherosclerotic plaques.
2022-11-04 | GSE197073 | GEO
Project description:Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC transdifferentiation into macrophage-like SMCs. Furthermore, during transdifferentiation, the SMCs' expression of PADI4 upregulating and SMC generated extracellular trap, a web-like structure, which plays key role in the development of atherosclerosis plaque. To reveal the potential mechanism of the SMC derived macrophages generated ETs surducing surrounding SMCs within the media of artery during the process of atherosclerosis plaque development, we utilized the dsDNA and H3CIT protein to stimuli the SMCs, the SMC stimulated with 0.2%BSA as coontrol group, we collect the cells and did RNA-sequencing between two groups to find the potential signaling pathway participating in the process
2022-11-04 | GSE197074 | GEO
Project description:Macrophage extracellular traps originated from the vascular smooth muscle cells play key roles in atherosclerosis progression.
| PRJNA808764 | ENA
Project description:Macrophage extracellular traps originated from the vascular smooth muscle cells play key roles in atherosclerosis progression [scRNA-seq]
| PRJNA808770 | ENA
Project description:Macrophage extracellular traps originated from the vascular smooth muscle cells play key roles in atherosclerosis progression [RNA-seq]
| PRJNA808769 | ENA
Project description:Extracellular DNA traps (ETs) represent an immune response by which cells release essential materials like chromatin and granular proteins. Previous studies have demonstrated that the transdifferentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. This study seeks to investigate the interaction between CD68+ VSMCs and the formation of ETs and highlight its function in atherosclerosis. Here we show that ETs are inhibited, and atherosclerotic plaque formation is alleviated in male Myh11CrePad4flox/flox mice undergoing an adeno-associated-virus-8 (AAV8) mediating overexpression of proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) injection and being challenged with a high-fat diet. Obvious ETs generated from CD68+ VSMCs are inhibited by Cl-amidine and DNase I in vitro. By utilizing VSMCs-lineage tracing technology and single-cell RNA sequencing (scRNA-seq), we demonstrate that the ETs from CD68+ VSMCs influence the progress of atherosclerosis by regulating the direction of VSMCs’ transdifferentiation through STING-SOCS1 or TLR4 signaling pathway. Vascular smooth muscle cells (VSMCs) are known for their fate plasticity in atherosclerosis plaque progression. Here, Zhai et al. show that extracellular traps generated from CD68 + VSMCs adversely contribute to plaque progression and highlight their unexpected role in plaque stability by regulating the direction of VSMC trans-differentiation.
| S-EPMC9723654 | biostudies-literature
Project description:Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. NETs are increased in diabetes and impair the resolution of inflammation during wound healing. Atherosclerosis resolution, a process resembling wound healing, is also impaired in diabetes. Thus, we hypothesized that NETs impede atherosclerosis resolution in diabetes by increasing plaque inflammation. Indeed, transcriptomic profiling of plaque macrophages from NET+ and NET- areas in low-density lipoprotein receptor-deficient (Ldlr-/-) mice revealed inflammasome and glycolysis pathway upregulation, indicating a heightened inflammatory phenotype. We found that NETs declined during atherosclerosis resolution, which was induced by reducing hyperlipidemia in nondiabetic mice, but they persisted in diabetes, exacerbating macrophage inflammation and impairing resolution. In diabetic mice, deoxyribonuclease 1 treatment reduced plaque NET content and macrophage inflammation, promoting atherosclerosis resolution after lipid lowering. Given that humans with diabetes also exhibit impaired atherosclerosis resolution with lipid lowering, these data suggest that NETs contribute to the increased cardiovascular disease risk in this population and are a potential therapeutic target.
| S-EPMC7205252 | biostudies-literature
Project description:A growing body of evidence suggests that neutrophil extracellular traps (NETs) critically contribute to the development of atherosclerosis. However, the detailed mechanism of how NETs promote atherogenesis remains unknown. In this study, we explored the role of NETs for promoting atherosclerosis by modulating the activity of autophagy in macrophages. NETs were effectively induced by a nicotine administration to the HL-60 cell-derived neutrophil-like cells. Treatment with NETs markedly suppressed both autophagosome formation and autophagosome-lysosome fusion in 7-ketocholesterol-treated macrophages, which are accompanied by the enhancement of inflammasome activity. NETs upregulate epidermal growth factor receptor (EGFR) activity, which enhances Beclin-1 phosphorylation of the tyrosine residues of Beclin-1 by EGFR, inhibits the PI3 kinase activity of the Beclin1-Vps34 complex, and suppresses autophagosome formation in macrophages. Furthermore, NET-induced activation of EGFR allows Rubicon to increase its expression, thereby suppressing autophagosome-lysosome fusion. In vivo experiments revealed that the suppression of NET formation by ablating peptidyl arginine deiminase-4 in neutrophil leukocytes resulted in the attenuation of atherosclerotic plaques in a nicotine-administered HFD-fed ApoE -/- mice. Taken together, these results suggest that NET-mediated EGFR-Beclin-1 signaling in the macrophages promotes atherogenesis by autophagy inhibition-mediated inflammasome activation.
| S-EPMC9340257 | biostudies-literature
Project description:BackgroundA new mechanism for intercellular communication has recently emerged that involves intercellular transfer of extracellular vesicles (EVs). Several studies have indicated that EVs may play a potential role in cell-to-cell communication between macrophage foam cells and vascular smooth muscle cells (VSMCs) in atherosclerotic lesion.Methods and resultsThis study involved the comparison of circulating EVs from atherosclerotic patients and control participants. The results showed that the circulation of the patients contained more leukocyte-derived EVs and that these EVs promoted more VSMC adhesion and migration than those of healthy participants. We then established a macrophage foam cell model and characterized the EVs from the macrophages. We used flow cytometric analyses and cell migration and adhesion assays and determined that the foam cells generated more EVs than the normal macrophages and that the foam cell-derived EVs were capable of promoting increased levels of VSMC migration and adhesion. Furthermore, we performed a proteomic analysis of the EVs. The data showed that the foam cell-derived EVs may promote VSMC adhesion and migration by regulating the actin cytoskeleton and focal adhesion pathways. In addition, Western blotting revealed that foam cell-derived EVs could promote the phosphorylation of ERK and Akt in VSMCs in a time-dependent manner. We also found that foam cell-derived EVs could enter the VSMCs and transfer integrins to the surface of these cells.ConclusionsThe data in our present study provide the first evidence that EVs from foam cells could promote VSMC migration and adhesion, which may be mediated by the integration of EVs into VSMCs and the subsequent downstream activation of ERK and Akt.
| S-EPMC5121506 | biostudies-literature
Project description:Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. In diabetes they are increased and impair wound healing, during which inflammation normally resolves. Atherosclerosis regression, a process resembling wound healing, is also impaired in diabetes. Thus, we hypothesized that NETs impede atherosclerosis regression in diabetes through unresolved inflammation. Objective: To investigate in diabetes the effect of NETs on plaque macrophage inflammation and whether NETs reduction improves atherosclerosis regression. Findings: Transcriptomic profiling of plaque macrophages from NET positive and negative areas in Ldlr-/- mice revealed inflammasome and glycolysis pathway upregulation, indicating a pro-inflammatory phenotype. During atherosclerosis regression in non-diabetic mice, plaque NET content decreased. In contrast, in diabetic mouse plaques NETs were enriched and persisted after lipid-lowering. DNase1 treatment (to degrade NETs) of diabetic mice reduced plaque NETs and macrophage inflammation and improved atherosclerosis regression after lipid-lowering. Conclusions: NETs decline during atherosclerosis regression in non-diabetic mice, but persist in diabetes and impair regression by exacerbating macrophage inflammation. DNase1 reduced diabetic plaque NETs and macrophage inflammation, and restored atherosclerosis resolution after lipid-lowering, despite ongoing hyperglycemia. Given that humans with diabetes also exhibit impaired atherosclerosis resolution with lipid-lowering, these data suggest that NETs contribute to the increased CVD risk in this population.
2020-05-12 | GSE145200 | GEO