Transcriptome analysis reveals non-foamy rather than foamy plaque macrophages are pro-inflammatory in atherosclerotic murine models
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE116271 | GEO | 2018/08/30
REPOSITORIES: GEO
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Project description:RationaleMonocyte infiltration into the subintimal space and its intracellular lipid accumulation are the most prominent features of atherosclerosis. To understand the pathophysiology of atherosclerotic disease, we need to understand the characteristics of lipid-laden foamy macrophages in the subintimal space during atherosclerosis.ObjectiveWe sought to examine the transcriptomic profiles of foamy and nonfoamy macrophages isolated from atherosclerotic intima.Methods and resultsSingle-cell RNA sequencing analysis of CD45+ leukocytes from murine atherosclerotic aorta revealed that there are macrophage subpopulations with distinct differentially expressed genes involved in various functional pathways. To specifically characterize the intimal foamy macrophages of plaque, we developed a lipid staining-based flow cytometric method for analyzing the lipid-laden foam cells of atherosclerotic aortas. We used the fluorescent lipid probe BODIPY493/503 and assessed side-scattered light as an indication of cellular granularity. BODIPYhiSSChi foamy macrophages were found residing in intima and expressing CD11c. Foamy macrophage accumulation determined by flow cytometry was positively correlated with the severity of atherosclerosis. Bulk RNA sequencing analysis showed that compared with nonfoamy macrophages, foamy macrophages expressed few inflammatory genes but many lipid-processing genes. Intimal nonfoamy macrophages formed the major population expressing IL (interleukin)-1β and many other inflammatory transcripts in atherosclerotic aorta.ConclusionsRNA sequencing analysis of intimal macrophages from atherosclerotic aorta revealed that lipid-loaded plaque macrophages are not likely the plaque macrophages that drive lesional inflammation.
| S-EPMC6945121 | biostudies-literature
Project description:Transcriptome analysis reveals non-foamy rather than foamy plaque macrophages are pro-inflammatory in atherosclerotic murine models
| PRJNA477941 | ENA
Project description:To elucidate the impact of Trem2 agonist on aortic gene expression during atherosclerosis.
2024-04-18 | GSE256189 | GEO
Project description:Trem2 Agonist Reprograms Foamy Macrophages to Promote Atherosclerotic Plaque Stability
| PRJNA1078390 | ENA
Project description:Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.
| S-EPMC10475825 | biostudies-literature
Project description:Aberrantly expressed miRNAs contribute to developmental abnormalities and diseases such as cancer, diabetes, and cardiovascular disorders, by hybridizing to specific mRNA targets and repressing their translation into proteins. Although miRNA expression signature is characterized in the process of neointimal thickening during proliferative vascular diseases such as atherosclerosis, so far global miRNA expression profiling in the different stages of atherosclerosis is completely unknown. We explored stage-specific microRNA signatures in the progress of atherosclerosis in hyperlipidemia mouse model, which may help to identify the critical miRNAs contributing atherosclerotic development and stabilization. Female apoe-/- mice (6-8 weeks, Jackson Laboratory) were fed a high fat diet (HFD, 21% crude fat, 0.15% cholesterol and 19.5% casein, Altromin, Germany) for 3 or 10 months (N=3-4). Serial sections (20 µm thick) of aortic roots and carotid arteries from these mice were mounted on membrane mounted metal frame slides (MMI), deparaffinized under RNase-free conditions, and completely dried. Laser capture microdissection (LCM) was performed with a laser microdissection system (MMI cellcut plus, Molecular Machines and Industries, Switzerland) assembled onto an inverted microscope (Olympus IX71). Plaque tissue or morphologically normal vessel wall of at least 40 sections per mouse were collected. RNA was isolated using RecoverAll total nucleic acid isolation kit (Applied Biosystems) according to the manufacturer’s instructions.
2013-03-27 | E-GEOD-34647 | biostudies-arrayexpress
Project description:Aberrantly expressed miRNAs contribute to developmental abnormalities and diseases such as cancer, diabetes, and cardiovascular disorders, by hybridizing to specific mRNA targets and repressing their translation into proteins. Although miRNA expression signature is characterized in the process of neointimal thickening during proliferative vascular diseases such as atherosclerosis, so far global miRNA expression profiling in the different stages of atherosclerosis is completely unknown. We explored stage-specific microRNA signatures in the progress of atherosclerosis in hyperlipidemia mouse model, which may help to identify the critical miRNAs contributing atherosclerotic development and stabilization.
2013-03-27 | GSE34647 | GEO
Project description:It has been observed that the consumption of litchi often causes symptoms characterized by itching or sore throat, gum swelling, oral cavity ulcers and even fever and inflammation, which significantly impair the quality of life of a large population. Using the RAW264.7 cell line, a step-by-step strategy was used to screen for the components in litchi fruits that elicited adverse reactions. The adverse reaction fractions were identified by mass spectrometry and analyzed using the SMART program, and a sequence alignment of the homologous proteins was performed. MTT tests were used to determine the cytotoxicity of a litchi protein extract in RAW264.7 macrophages, and real-time PCR was applied to analyze the expression of inflammatory genes in the RAW264.7 cells treated with lipopolysaccharide or the litchi protein extract. The results showed that the litchi water-soluble protein extract could increase the production of the pro-inflammatory mediators IL-1β, iNOS and COX-2, and the anti-inflammatory mediator HO-1 in the RAW264.7 cell line. The 14-3-3-like proteins GF14 lambda, GF14 omega and GF14 upsilon were likely the candidate proteins that caused the adverse effects.
| S-EPMC4855250 | biostudies-literature
Project description:Despite abundant research demonstrating that platelets can promote tumor cell metastasis, whether primary tumors affect platelet-producing megakaryocytes remains understudied. In this study, we used a spontaneous murine model of breast cancer to show that tumor burden reduced megakaryocyte number and size and disrupted polyploidization. Single-cell RNA sequencing demonstrated that megakaryocytes from tumor-bearing mice exhibit a pro-inflammatory phenotype, epitomized by increased Ctsg, Lcn2, S100a8, and S100a9 transcripts. Protein S100A8/A9 and lipocalin-2 levels were also increased in platelets, suggesting that tumor-induced alterations to megakaryocytes are passed on to their platelet progeny, which promoted in vitro tumor cell invasion and tumor cell lung colonization to a greater extent than platelets from wild-type animals. Our study is the first to demonstrate breast cancer-induced alterations in megakaryocytes, leading to qualitative changes in platelet content that may feedback to promote tumor metastasis.
| S-EPMC9555784 | biostudies-literature
Project description:BackgroundP2Y(6), a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6) deficiency on atherosclerosis.Methodology/principal findingsCell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6) receptors, showed that exogenous expression of P2Y(6) induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6)-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6) and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6) in atherosclerotic lesion development, we used P2Y(6)-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6) receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6)xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6) deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice.ConclusionsP2Y(6) receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6) deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6) in vascular disease pathophysiologies, such as aneurysm formation.
| S-EPMC4216081 | biostudies-literature