Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells (gene expression)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30780 | GEO | 2011/07/20
SECONDARY ACCESSION(S): PRJNA144309
REPOSITORIES: GEO
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Project description:We report that hyperglycemia-mediated induction of genes and pathways associated to endothelial dysfunction occur through modulation of acetylated H3K9/K14 inversely correlated with methyl-CpG content. Examination of H3K9/K14 histone acetylation and DNA methylation in hyperglycemic conditions.
2011-06-01 | E-GEOD-29251 | biostudies-arrayexpress
Project description:We report that hyperglycemia-mediated induction of genes and pathways associated to endothelial dysfunction occur through modulation of acetylated H3K9/K14 inversely correlated with methyl-CpG content. Examination of H3K9/K14 histone acetylation and DNA methylation in hyperglycemic conditions. see GSE29251 for histone acetylation and DNA methylation
2011-07-19 | E-GEOD-30780 | biostudies-arrayexpress
Project description:We report that hyperglycemia-mediated induction of genes and pathways associated to endothelial dysfunction occur through modulation of acetylated H3K9/K14 inversely correlated with methyl-CpG content.
2011-06-01 | GSE29251 | GEO
Project description:Emerging evidence suggests that poor glycemic control mediates post-translational modifications to the H3 histone tail. We are only beginning to understand the dynamic role of some of the diverse epigenetic changes mediated by hyperglycemia at single loci, yet elevated glucose levels are thought to regulate genome-wide changes, and this still remains poorly understood. In this article we describe genome-wide histone H3K9/K14 hyperacetylation and DNA methylation maps conferred by hyperglycemia in primary human vascular cells. Chromatin immunoprecipitation (ChIP) as well as CpG methylation (CpG) assays, followed by massive parallel sequencing (ChIP-seq and CpG-seq) identified unique hyperacetylation and CpG methylation signatures with proximal and distal patterns of regionalization associative with gene expression. Ingenuity knowledge-based pathway and gene ontology analyses indicate that hyperglycemia significantly affects human vascular chromatin with the transcriptional up-regulation of genes involved in metabolic and cardiovascular disease. We have generated the first installment of a reference collection of hyperglycemia-induced chromatin modifications using robust and reproducible platforms that allow parallel sequencing-by-synthesis of immunopurified content. We uncover that hyperglycemia-mediated induction of genes and pathways associated with endothelial dysfunction occur through modulation of acetylated H3K9/K14 inversely correlated with methyl-CpG content.
| S-EPMC3202278 | biostudies-literature
Project description:Hyperglycemia is a hallmark in prediabetes and type 2 diabetes mellitus (T2DM) which increases risk of micro and macrovascular complications such as diabetic retinopathy, diabetic nephropathy (microvascular complications), and peripheral vascular disease, cerebrovascular disease and cardiovascular diseases (macrovascular complications). Endothelial cells are affected in both cases. In this study, we investigated the miRNA expression changes in HUVECs during different glucose treatment (5mM, 10mM, 25mM and 40mM glucose) at various time intervals (6, 12, 24 and 48hrs). The results of miRNA microarray showed there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico prediction showed that the following pathways: Regulation of actin cytoskeleton, PI3K-Akt signaling pathway, Apoptosis, Neurotrophin signaling pathway, and Insulin signaling pathway, were dysregulated during hyperglycemia. Majority of the pathways are related to apoptosis. 10 miRNAs (miR-26a-5p, -26b-5p, 29b-3p, 29c-3p, 125b-1-3p, -130b-3p, - 140-5p, -221-3p, -192-5p, and -320a,) showed increased expression with increasing concentration of glucose treatment. miR-26a-5p, -29b-3p, - 140-5p, -221-3p, and -192-5p are involves in endothelial apoptosis. Our study revealed miRNAs (miR-29b-3p and – 192-5p) with known mRNA targets (BCL2 and MCL1) showed expression pattern inversely correlating with their respective target mRNAs. Therefore these miRNAs could involve in the endothelial dysfunction due to hyperglycemia.
2016-05-23 | GSE74296 | GEO
Project description:Purpose:To take a comprehensive effort in characterizing the brain vasculature gene expression upon hyperglycemia. Methods: We extracted mRNA from brain microvasculature fragments isolated from a genetic mouse model of hyperglycemia (Ins2-AKITA) and WT mice and analyzed their transcriptome with RNA sequencing The samples were sequenced on an Illumina HiSeq 2500 sequencer at the SNP&SEQ sequencing facility (Science for Life laboratory (SciLifeLab), Uppsala sequencing node). The reads were aligned to the Ensembl mouse gene assembly (NCBIM37) using Tophat2 software (version 2.0.4). The duplicated reads were removed using the picard tool (version 1.92). To identify the genes significantly enriched in the pericyte samples as compared with microvascular samples, statistical tests were performed using the Cufflinks tool (version 2.2.1) Results: Twenty-three genes were significantly regulated in mutant when compared to WT (False Discovery Rate < 0.05)
2018-12-11 | GSE113919 | GEO
Project description:Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic β-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina. Intravitreal (5ug or 10ug) or subcutaneous (30mg/kg) injection of STZ at the early stage of newborn rats couldn’t induce hyperglycemia but caused NSIR (neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn’t induce NSIR when all retinal progenitors exit the cell cycle. Thus, NSIR in rats is independent of hyperglycemia but due to STZ’s direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.
2024-07-16 | GSE272311 | GEO
Project description:Brain vascular transcriptomes of mouse hyperglycemia mutants and controls
| PRJNA454465 | ENA
Project description:Skeletal muscle of insulin resistant individuals is characterized by lower fasting lipid oxidation and reduced ability to switch between lipid and glucose oxidation. The purpose of the present study was to examine if impaired metabolic switching could be induced by chronic hyperglycemia. Human myotubes were treated with or without chronic hyperglycemia (HG) (20 mmol/l glucose for 4 days), and the metabolism of [14C]oleic acid (OA) and [14C]glucose was studied. Acute glucose (5mmol/l) suppressed OA oxidation by 50% in normoglycemic (NG) (5.5 mmol/l glucose) cells. Myotubes exposed to chronic hyperglycemia showed a significantly reduced OA uptake and oxidation to CO2, whereas acid-soluble metabolites were increased. Glucose suppressibility, the ability of acute glucose to suppress lipid oxidation, was significantly reduced to 21%, while adaptability, the capacity to increase lipid oxidation with increasing fatty acid availability, was unaffected. Glucose uptake and oxidation was significantly reduced by about 40%. Substrate oxidation in presence of mitochondrial uncouplers showed that net and maximal oxidative capacities were significantly reduced after hyperglycemia, and the concentration of ATP was reduced by 25%. However, none of the measured mitochondrial genes were downregulated nor was mitochondrial content. Microarray showed that no genes were significantly regulated by chronic hyperglycemia. Addition of chronic lactate reduced both glucose and OA oxidation to the same extent as hyperglycemia, and this effect was specific for lactate. In conclusions, chronic hyperglycemia reduced substrate oxidation in skeletal muscle cells and impaired the metabolic switching. The effect is most likely due to an induced mitochondrial dysfunction.
2009-12-24 | GSE19620 | GEO
Project description:Diabetes is associated with a more aggressive form of atherosclerosis. Thrombospondin-1 (TSP-1), an extracellular matrix protein, is an acute phase reactant that induces vascular smooth muscle (VSMC) migration and proliferation in areas of vascular injury, and is also upregulated in VSMCs exposed to hyperglycemia. We hypothesized that hyperglycemia amplifies the expression of genes induced by TSP-1 in VSMCs. Human aortic VSMCs were cultured in DMEM supplemented with 10 % FBS and 1% antibiotics, cells were used between passages three and five. VSMCs were preincubated in DMEM containing 0.2% FBS with 5 mM glucose (normoglycemia), 25 mM glucose (hyperglycemia), 25 mM mannose (osmotic control), TSP-1 (20µg/mL), 25 mM glucose + TSP-1 (20µg/mL) or 25 mM mannose + TSP-1 (20µg/mL). Data analysis revealed that TSP-1 stimulates gene expression relevant to the pathogenesis of atherosclerosis and diabetic vascular disease. Total RNA was extracted from replicate cultures of human aortic VSMCs and microarray analysis performed for a total of 18 samples (3 replicates per condition) using the Human Gene Array ST.
2009-08-11 | E-GEOD-17556 | biostudies-arrayexpress