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PROVIDER: PRJNA1135337 | ENA |
REPOSITORIES: ENA
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Project description:Atherosclerosis (AS) is one of the most common diseases in middle-age and elderly population. Lipid metabolism disorder induced foaming of vascular smooth muscle cell (VSMC) is an important pathological process of AS. Mitochondria plays an important role in lipids metabolism. While it is not known whether regulating mitochondrial function can protect ox-LDL induced VSMC foaming via metabolic reprogramming. With ox-LDL induced mouse model of VSMC injury, the injury effect of ox-LDL and the protective effect of mdivi-1, the mitochondrial fission inhibitor on mitochondrial morphology and function of VSMC, and the formation of lipid droplet were observed. With metabonomics and proteomics techniques, the main lipid metabolites and regulation proteins were identified. The results showed that Ox-LDL induced a significant mitochondrial fission and fragmentation of VSMC, and mitochondrial function disorder along with lipid deposition and foaming. Mdivi-1 significantly antagonized the damage effect of ox-LDL on mitochondrial morphology and function of VSMC, and blocked the lipid deposition. Metabonomics analysis found 848 different metabolites between ox-LDL and mdivi-1 treatment group, in which the lipid metabolites were the main, and heptadecanoic acid, palmitoleic acid and myristic acid were the critical metabolites changed most. Proteomics results showed that there were 125 differential expressed proteins between ox-LDL and mdivi-1 treatment, acetyl -CoA carboxylase1 and fatty acid synthase were the main differential expressed proteins. This study suggest that Mitochondrial fission plays an important role in VSMC lipid deposition and foaming. Inhibition of mitochondrial fission may effectively fight against ox-LDL induced lipid deposition and foaming of VSMC via improving mitochondrial function and metabolic reprogramming. This finding provides a new insight for prevention and treatment of AS.
2022-10-14 | PXD035671 | Pride
Project description:Early transcriptomic response to n-LDL and ox-LDL in human vascular smooth muscle cells (hVSMC). We used microarrays with the aim of assessing early molecular changes that induce a response in the VSMC using native and oxidized low-density lipoprotein (n-LDL and ox-LDL).
2016-02-09 | GSE68021 | GEO
Project description:Background: The co-stimulatory CD40-CD40L dyad is an important driver of atherosclerosis. CD40 exerts divergent, cell-specific roles, which differentially impact atherogenesis. Objectives: We here investigate the role of the most prominent CD40-expressing cell-type, the B-cell, in atherosclerosis. Methods: B-cell subset specific CD40-expression of patients with mild and severe coronary artery disease (CAD) was determined by mass-cytometry and correlated to CAD severity. Underlying mechanisms were elucidated using B-cell CD40-deficient CD19Cre-CD40flfl-ApoE-/-(CD40BKO) mice and control littermates (CD40BWT). Results: Patients with severe CAD had similar CD40 expression levels on most B-cell subsets but showed a profound decrease in CD40 on putative B1 cells. This was associated with increased atherosclerotic plaque burden and decreased plaque fibrosis. Likewise, CD40BKO mice exhibited an increased plaque area and more advanced staging of atherosclerosis. Absence of CD40 on B-cells caused a decrease in immunoglobulin (Ig) producing cells, including germinal center-, plasma-, but especially B1 cells, thereby reducing levels of (anti-ox/MDA-LDL) IgG and protective (anti-ox/MDA-LDL) IgM. Transcriptomics analysis revealed that the absence of CD40 on B1b cells caused altered gene expression pathways related to lipid uptake (Cd36, Ldlr), cellular stress and metabolism (Nr4a1, Hif1a), and cell death (Naip5/6, Ccnd2). Indeed, in vitro analysis showed that B1bCD40KO cells took up excessive amounts of ac/oxLDL, exhibited defective BCR signaling, and were prone to apoptosis, especially in hyperlipidemic conditions. Transfer of wild-type B1b cells in CD40BKO mice prevented the increase in atherosclerosis. Conclusions: Patients with severe CAD had similar CD40 expression levels on most B-cell subsets but showed a profound decrease in CD40 on putative B1 cells. This was associated with increased atherosclerotic plaque burden and decreased plaque fibrosis. Likewise, CD40BKO mice exhibited an increased plaque area and more advanced staging of atherosclerosis. Absence of CD40 on B-cells caused a decrease in immunoglobulin (Ig) producing cells, including germinal center-, plasma-, but especially B1 cells, thereby reducing levels of (anti-ox/MDA-LDL) IgG and protective (anti-ox/MDA-LDL) IgM. Transcriptomics analysis revealed that the absence of CD40 on B1b cells caused altered gene expression pathways related to lipid uptake (Cd36, Ldlr), cellular stress and metabolism (Nr4a1, Hif1a), and cell death (Naip5/6, Ccnd2). Indeed, in vitro analysis showed that B1bCD40KO cells took up excessive amounts of ac/oxLDL, exhibited defective BCR signaling, and were prone to apoptosis, especially in hyperlipidemic conditions. Transfer of wild-type B1b cells in CD40BKO mice prevented the increase in atherosclerosis.
2024-10-19 | GSE186134 | GEO
Project description:Early transcriptomic response to n-LDL and ox-LDL in human vascular smooth muscle cells (hVSMC). We used microarrays with the aim of assessing early molecular changes that induce a response in the VSMC using native and oxidized low-density lipoprotein (n-LDL and ox-LDL). For each LDL internalization experiment, three biological replicates were used and the samples pooled with the aim of obtain three technical replicates (three arrays for condition).
2016-02-09 | E-GEOD-68021 | biostudies-arrayexpress
Project description:Since previous stduies demostrated that oxidized phospholipids function as caspase-11 agonists to induce noncanonical inflammasome activation in immune cells and the levels of oxidized phospholipids derived from ox-LDL are largely elevated in atherosclerotic lesions. Purpose:RNA-Sequencing analysis of ox-LDL-treated peritoneal macrophages transcriptomes.Methods and results:The principal component analysis gene expression profiles of the control and ox-LDL-treated groups were clearly distinct. Among the DEGs that met the cutoff criteria of a -log10(false discovery rate (FDR)) > 2 and |log2(fold change (FC)| > 2. A total of 1,388 downregulated and 855 upregulated genes were identified. GSEA showed that the dominant upregulated pathways in ox-LDL-treated macrophages were associated with the IL-1-mediated signaling pathway, response to cytokine stimulus, and granulocyte migrationwe discovered that caspase-11-mediated inflammation signaling was significantly activated in ox-LDL-treated peritoneal macrophages.Conclusions：we verified caspase11associated inflammatory signaling was significantly activated in ox-LDL-treated macrophages.
2021-05-19 | GSE171413 | GEO
Project description:LDL or Ox-LDL 200ug/ml, which showed no loss of viability after a 48 hour exposure, induced a physiological and pathological transcriptional response, respectively. LDL induced a downregulation of genes associated with cholesterol biosynthesis while ox-LDL induced transcriptional alterations in genes related to inflammation, matrix expansion, lipid metabolism and processing, and apoptosis. Pentraxin-3 was secreted into the culture medium after RPE cells were stimulated with ox-LDL, and immunohistochemically evident in Bruchs membrane of human macular samples with age-related macular degeneration. ARPE-19 cells exposed to 200ug/ml ox-LDL had a 38% apoptosis rate compared to less than 1% when exposed to LDL or untreated controls (p<0.0001). While LDL induced a physiologic response by RPE cells, a pathological phenotypic response was seen after treatment with oxidatively modified LDL. The transcriptional, biochemical, and functional data provide initial support of a role for the hypothesis that modified LDLs are one trigger for initiating events that contribute to the development of age-related macular degeneration. Keywords: treatment with non-treatment control Human ARPE-19 cells were exposed to LDL or oxidatively modified LDL (ox-LDL) for 48 hours for RNA extraction and hybridization on Affymetrix microarrays. We sought to determine whether retina, pigment epithelial cells develop a pathologic phenotype after exposure to low density lipoproteins (LDL) that are oxidatively modified.We have made two comparsions: LDL treatment versus non-treatment; ox-LDL treatment versus non-treatment.
2006-09-01 | E-GEOD-5741 | biostudies-arrayexpress
Project description:Oxidized low-density lipoprotein (ox-LDL) can impair endothelial function and lead to the development of atherosclerosis. Protein S-nitrosylation is sensitive to the cellular redox state and acts as a crucial regulator and executor of NO signaling pathways. Aberrant S-nitrosylation contributes to the pathogenesis of cardiovascular and cerebrovascular diseases. However, the effect of ox-LDL on S-nitrosylation and its significance for endothelial dysfunction have not been studied at the S-nitrosylation proteome level. In our study, many key proteins belonged to ribosomal structure and translational regulatory proteins, covering the entire translation process. These results indicated that S-nitrosylation of the translational machinery in vascular endothelial cells was susceptible to ox-LDL.
2018-04-04 | PXD009386 |
Project description:Target genes regulated by ox-LDL treatment in bladder cancer cells T24 were identified by microarrays. In this dataset, we include the expression data obtained from bladder cancer cells T24 starved with serum-free medium and then treated with 20 μg/mL ox-LDL or vehicle for 24 h. These data are used to obtain genes that are differentially expressed in response to ox-LDL treatment.
2022-02-18 | GSE134530 | GEO
Project description:LDL or Ox-LDL 200ug/ml, which showed no loss of viability after a 48 hour exposure, induced a physiological and pathological transcriptional response, respectively. LDL induced a downregulation of genes associated with cholesterol biosynthesis while ox-LDL induced transcriptional alterations in genes related to inflammation, matrix expansion, lipid metabolism and processing, and apoptosis. Pentraxin-3 was secreted into the culture medium after RPE cells were stimulated with ox-LDL, and immunohistochemically evident in Bruch’s membrane of human macular samples with age-related macular degeneration. ARPE-19 cells exposed to 200?g/ml ox-LDL had a 38% apoptosis rate compared to less than 1% when exposed to LDL or untreated controls (p<0.0001). While LDL induced a physiologic response by RPE cells, a pathological phenotypic response was seen after treatment with oxidatively modified LDL. The transcriptional, biochemical, and functional data provide initial support of a role for the hypothesis that modified LDLs are one trigger for initiating events that contribute to the development of age-related macular degeneration. Keywords: treatment with non-treatment control
2006-09-01 | GSE5741 | GEO
Project description:Analysis of the effect of a bacterial quorum sensing molecule on in-vitro culture of human endothelial cells at gene expression levels. Objective: Chronic infection has long been postulated as a stimulus for atherogenesis. Pseudomonas aeruginosa infection has been associated with increased atherosclerosis in rats, and the bacteria produce a quorum sensing molecule 3-oxo-dodecynoyl-homoserine lactone (3OC12-HSL) that is critical for colonization and virulence. Paraoxonase 2 (PON2) hydrolyzes 3OC12-HSL and also protects against the effects of oxidized phospholipids thought to contribute to atherosclerosis. We now report the response of human aortic endothelial cells (HAEC) to 3OC12-HSL and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC) in relation to PON2 expression. Methods and Results: Using expression profiling and network modeling, we identified the unfolded protein response (UPR), cell cycle genes, and the MAPK signaling pathway to be heavily involved in the HAEC response to 3OC12-HSL. The network also showed striking similarities to a network created based on HAEC response to Ox-PAPC, a major component of minimally-modified LDL. HAEC in which PON2 was silenced by siRNA showed increased pro-inflammatory and UPR responses when treated with 3OC12-HSL or Ox-PAPC. Conclusion: 3OC12-HSL and Ox-PAPC influence similar inflammatory pathways. Quorum sensing molecules such as 3OC12-HSL contribute to the pro-atherogenic effects of chronic infection and the anti-atherogenic effects of PON2 include destruction of quorum sensing molecules. 4 HAEC lines from different donors were treated with 3-O-C12 HSL or control (medium).
2010-12-30 | E-GEOD-26295 | biostudies-arrayexpress