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 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: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: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: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
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:Although various types of drugs and therapies are available to treat atherosclerosis, it remains a major cause of mortality throughout the world. Macrophages are the major source of foam cells, which are hallmarks of atherosclerotic lesions. Consequently, the roles of macrophages in the pathophysiology of atherosclerosis are increasingly investigated. Autophagy is a self-protecting cellular catabolic pathway. Since its discovery, autophagy has been found to be associated with a variety of diseases, including cardiovascular diseases, malignant tumors, neurodegenerative diseases, and immune system disorders. Accumulating evidence demonstrates that autophagy plays an important role in inhibiting inflammation and apoptosis, and in promoting efferocytosis and cholesterol efflux. These facts suggest the induction of autophagy may be exploited as a potential strategy for the treatment of atherosclerosis. In this review we mainly discuss the relationship between macrophage autophagy and atherosclerosis and the molecular mechanisms, as well as the recent advances in targeting the process of autophagy to treat atherosclerosis.
| S-EPMC4753375 | biostudies-other
Project description:Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Neutrophils are a component of the innate immune system which protect against pathogen invasion; however, the contribution of neutrophils to cardiovascular disease has been underestimated, despite infiltration of leukocyte subsets being a known driving force of atherosclerosis and thrombosis. In addition to their function as phagocytes, neutrophils can release their extracellular chromatin, nuclear protein, and serine proteases to form net-like fiber structures, termed neutrophil extracellular traps (NETs). NETs can entrap pathogens, induce endothelial activation, and trigger coagulation, and have been detected in atherosclerotic and thrombotic lesions in both humans and mice. Moreover, NETs can induce endothelial dysfunction and trigger proinflammatory immune responses. Overall, current data indicate that NETs are not only present in plaques and thrombi but also have causative roles in triggering formation of atherosclerotic plaques and venous thrombi. This review is focused on published findings regarding NET-associated endothelial dysfunction during atherosclerosis, atherothrombosis, and venous thrombosis pathogenesis. The NET structure is a novel discovery that will find its appropriate place in our new understanding of cardiovascular disease. In addition, NETs have high potential to be further explored toward much better treatment of atherosclerosis and venous thromboembolism in clinic.
| S-EPMC5545592 | biostudies-other
Project description:[Figure: see text].
| S-EPMC8442908 | biostudies-literature
Project description:BackgroundCoronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood.MethodsSamples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.Patient findingsHere, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage.InterpretationThese data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.FundingDeutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung.
| S-EPMC7397705 | biostudies-literature
Project description:Human neutrophils have been known to release neutrophil extracellular traps (NETs), antimicrobial DNA structures capable of capturing and killing microbes. Recently, a similar phenomenon has been reported in macrophages infected with various pathogens. However, a role for macrophages extracellular traps (METs) in host defense responses against Mycobacterium massiliense (M. mass) has yet to be described. In this study, we show that M. mass, a rapid growing mycobacterium (RGM), also induces the release of METs from PMA-differentiated THP-1 cells. Intriguingly, this process is not dependent on NADPH oxidase activity, which regulates NET formation. Instead, M. mass-induced MET formation partially depends on calcium influx and requires phagocytosis of high bacterial load. The METs consist of a DNA backbone embedded with microbicidal proteins such as histone, MPO and elastase. Released METs entrap M. mass and prevent their dissemination, but do not have bactericidal activity. Instead, they result in enhanced bacterial growth. In this regard, METs were considered to provide interaction of M. mass with cells and an environment for bacterial aggregation, which may facilitate mycobacterial survival and growth. In conclusion, our results demonstrate METs as an innate defense response against M. mass infection, and suggest that extracellular traps play a multifaceted role in the interplay between host and bacteria.
| S-EPMC4871462 | biostudies-literature