Rates of LDL entry and retention in mouse aorta are dissociated and predict the course of atherogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE210096 | GEO | 2022/08/05
REPOSITORIES: GEO
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Project description:Rates of LDL entry and retention in mouse aorta are dissociated and predict the course of atherogenesis
| PRJNA863649 | ENA
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: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: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: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:Electronegative LDL (LDL(-)) is a minor modified fraction of human plasma LDL with several atherogenic properties. Among them, LDL(-) has increased content of bioactive lipid mediators, such as lysophosphatidylcholine (LPC), non-esterified fatty acids (NEFA), ceramide (Cer), and sphingosine (Sph), which are related to the presence in LDL(-) of some phospholipolytic activities, including platelet-activating factor acetylhydrolase (PAF-AH), phospholipase C (PLC) and sphingomyelinase (SMase). However, the activity of these enzymes does not explain the increased content of Sph, which should derive from Cer degradation. In the present study we analyzed the putative presence of a ceramidase (CDase) activity that could explain the increased content of Sph. Thin layer chromatography (TLC) and lipidomic analysis showed that Cer, Sph and NEFA spon-taneously increased in LDL(-) incubated alone at 37ºC, in contrast with native LDL(+). An inhibitor of neutral CDase prevented the formation of Sph and, in contrast, increased the content of Cer in LDL(-). In addition, a fluorescently-labelled Cer (NBD-Cer) was efficiently degraded by LDL(-) to form Sph and NEFA. These observations point to the existence of a CDase activity associated to LDL(-). However, neither proteomic analysis nor western blot detected the presence of a known CDase enzyme. Further studies are warranted to define the origin of the CDase activity detected in LDL(-).
2023-01-09 | PXD036168 | Pride
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:We report that bone marrow transplantation suppresses atherosclerosis by reducing LDL accumulation in the intima. Radiation exposure enhances endothelial endolysosomal trafficking and cholesterol efflux pathways, thus preventing reducing the abundance of LDL particles that traverse the endothelial layer to deposit in the sub-endothelial space.
2021-03-31 | GSE163206 | GEO
Project description:To investigate gene expression after treatment of LL37 and LDL, we treated THP-1 macropahges with LL37 and/ or LDL.
2023-06-10 | GSE230360 | GEO
Project description:Although the mechanisms underlying development of atherosclerosis are not well understood, LDL-C is known to influence expression of endothelial microRNAs (miRNAs) and gene-targets of miRNAs to promote cell senescence. However, the impact of LDL-C on expression of PBMC miRNAs and miRNA targeted genes in response to an atherogenic diet is not known. We hypothesized that miRNA expression profiles differ between baboons with low and high serum low-density lipoprotein cholesterol (LDL-C) concentrations in response to diet, and that microRNA-gene networks in baboons discordant for LDL-Cholesterol We generated small RNA libraries from baboons differing in their LDL-C response to dietary fat and cholesterol (low LDL-C, n = 3; high LDL-C, n = 3) using liver biopsies collected before and after a high-cholesterol, high-fat (HCHF) challenge diet. We sequenced the libraries using Next-Generation Illumina sequencing methods, analyzed the data using mirTools software and identified 517 baboon miRNAs: 490 homologous to human and 27 novel miRNAs. HCHF diet elicited expression of more miRNAs compared to baseline (chow) diet for both low and high LDL-C baboons. Seventeen miRNAs exhibited significant differential expression in response to HCHF diet in high LDL-C baboons compared to nine miRNAs in low LDL-C baboons. Putative miRNA targets were identified with TargetScan/Base tools. miRNAs significantly targeted more genes in high LDL-C baboons compared to low LDL-C responders. Further, we identified miRNA isomers and other non-coding RNAs that were differentially expressed in response to the challenge diet.Our discovery of differentially expressed baboon miRNAs and their targets is a fundamental step in understanding the role of non-coding RNAs in the modulation of dsylipidemia.
2019-03-20 | GSE114722 | GEO