The poloxamer P-407 chronic hyperlipidemia mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE6305 | GEO | 2006/11/22
SECONDARY ACCESSION(S): PRJNA100507
REPOSITORIES: GEO
Similar Datasets
Project description:We performed a systemic study of the poloxamer P-407-induced chronic hyperlipidemia in C57BL/6J mice. Mice were treated 96 days every third day.The poloxamer mostly elevates plasma triglycerides and cholesterol while change of the liver cholesterol is not significant. Experiment Overall Design: A group of 12 mice were administered 0.5 g/kg poloxamer P-407 by intraperitoneal (i.p.) injection (poloxamere group), a control group of 4 mice were injected every third day with normal saline. Total RNA from P-407 treated 12 mice has been pooled into 3 biological replicas (Smpl1, Smpl2 and Smpl3). Reference total RNA has been obtained by pooling 4 mice from control group. Each RNA sample has been splitted and hybridised in parallel on cDNA (G4104A) and oligonucleotide (G4120A) mouse microarrays (Agilent Technologies, CA, USA.
2008-06-14 | E-GEOD-6305 | biostudies-arrayexpress
Project description:Hyperlipidemia is accompanied by increased systemic inflammation. However, how hyperlipidemia affects T cell biology is still unclear. We aimed to detail the effects of hyperlipidemia on the T cell’s transcriptome, metabolome and lipidome. Low-density lipoprotein receptor-deficient (LDLR-/-) mice were subjected to a 0.15% high cholesterol diet (HCD), a normal chow diet (NCD) and T cells were analyzed. Hyperlipidemia induced an increase in CXCR3 on and IFN in CD4+ T cells, which was accompanied by transcriptomic changes in interleukin-mediated JAK/STAT signaling, interferon-γ signaling and a general pro-inflammatory immune response, suggesting that hyperlipidemia induces a Th1-like response. In these T cells, hyperlipidemia did not affect levels of metabolites involved in glycolysis or fatty acid oxidation, but enhanced amino acids levels. CD4+ T-cells of mice fed a HCD exhibited increased cellular cholesterol accumulation and an increased arachidonic acid (AA) to Docosahexaenoic acid (DHA) ratio, which was associated with T cell activation and IFN signaling. In vitro, T cell exposure to VLDL, but not LDL phenocopied these results. The effect of hyperlipidemia on T cell activation is reversible as transcriptional- and lipid profiles in LDLr-/ mice normalized 6 weeks after switching the HCD to NCD. In conclusion, hyperlipidemia induces a Th1-like response in CD4+ T cells, which is associated with an AA/DHA ratio in these cells. VLDL, but not LDL is the main lipid component driving hyperlipidemia induced T cell activation.
2023-03-29 | GSE196970 | GEO
Project description:Miniature pigs are useful model animal for gene expression studies on dietary-induced hyperlipidemia, because they have similar digestive physiology to human. Two typical dietary components were used for dietary-induced hyperlipidemia miniature pig models. One is a high-fat and high-cholesterol diet (HFCD) containing 15% lard and 2% cholesterol, the other is a high-fat, high-cholesterol and high-sucrose diet (HFCSD) containing 15% lard, 2% cholesterol and 37% sucrose.
2012-04-25 | GSE32616 | GEO
Project description:Miniature pigs are useful model animal for gene expression studies on dietary-induced hyperlipidemia, because they have similar digestive physiology to human. Two typical dietary components were used for dietary-induced hyperlipidemia miniature pig models. One is a high-fat and high-cholesterol diet (HFCD) containing 15% lard and 2% cholesterol, the other is a high-fat, high-cholesterol and high-sucrose diet (HFCSD) containing 15% lard, 2% cholesterol and 37% sucrose. Whole blood gene expression in HFCD, HFCSD and control male miniature pigs was measured at 10, 19 and 27 weeks of feeding periods.M-cM-^@M-^@White blood cell gene expression in HFCD, HFCSD and control male miniature pigs was measured at 27 weeks of feeding period.
2012-04-24 | E-GEOD-32616 | biostudies-arrayexpress
Project description:Hyperlipidemia is accompanied by increased systemic inflammation. However, how hyperlipidemia affects T cell biology is still unclear. We aimed to detail the effects of hyperlipidemia on the T cell’s transcriptome, metabolome and lipidome. Low-density lipoprotein receptor-deficient (LDLR-/-) mice were subjected to a 0.15% high cholesterol diet (HCD), a normal chow diet (NCD) and T cells were analyzed. Hyperlipidemia induced an increase in CXCR3 on and IFN in CD4+ T cells, which was accompanied by transcriptomic changes in interleukin-mediated JAK/STAT signaling, interferon-γ signaling and a general pro-inflammatory immune response, suggesting that hyperlipidemia induces a Th1-like response. In these T cells, hyperlipidemia did not affect levels of metabolites involved in glycolysis or fatty acid oxidation, but enhanced amino acids levels. CD4+ T-cells of mice fed a HCD exhibited increased cellular cholesterol accumulation and an increased arachidonic acid (AA) to Docosahexaenoic acid (DHA) ratio, which was associated with T cell activation and IFN signaling. In vitro, T cell exposure to VLDL, but not LDL phenocopied these results. The effect of hyperlipidemia on T cell activation is reversible as transcriptional- and lipid profiles in LDLr-/ mice normalized 6 weeks after switching the HCD to NCD. In conclusion, hyperlipidemia induces a Th1-like response in CD4+ T cells, which is associated with an AA/DHA ratio in these cells. VLDL, but not LDL is the main lipid component driving hyperlipidemia induced T cell activation.
2023-03-29 | GSE196971 | GEO
Project description:Hyperlipidemia and T cell driven inflammation are important drivers of atherosclerosis, the principal underlying cause of cardiovascular disease. Here, we applied an in-depth multi-omics approach to detail the effects of hyperlipidemia on T cells. In vitro, exposure of CD4+ T cells to very low-density lipoprotein (VLDL), but not to low-density lipoprotein (LDL) resulted in upregulation of Th1 associated pathways, suggesting that VLDL serves as the main lipid component driving hyperlipidemia induced T cell activation. To further detail this response in vivo, T-cells of ldlr-/- fed a normal cholesterol or high cholesterol diet, which develop a strong increase in VLDL cholesterol and triglyceride levels, were investigated. CD4+ T cells of hyperlipidemic ldlr-/- mice exhibited an increased expression of CXC-chemokine receptor 3 (CXCR3) and produced more TNFα and interferon-γ (IFN-γ). Gene set enrichment analysis identified IFN-γ-mediated signaling as the most upregulated pathway in hyperlipidemic T cells. However, the classical Th1 associated transcription factor profile with strong upregulation of Tbet and downregulation of Gata3 was not observed. Hyperlipidemia did not affect levels of the CD4+ T-cell’s metabolites involved in glycolysis or other canonical metabolic pathways but enhanced amino acids levels. However, CD4+ T-cells of hyperlipidemic mice showed increased cellular cholesterol accumulation and an increased arachidonic acid (AA) to docosahexaenoic acid (DHA) ratio, which was associated with T cell activation and IFN-γ-mediated signaling. In conclusion, hyperlipidemia, and especially its VLDL component induces an atypicial Th1 response in CD4+ T-cells.
2023-04-03 | GSE201598 | GEO
Project description:Hyperlipidemia is a well-established risk factor for cardiovascular diseases. Trillions of people worldwide display mildly elevated levels of plasma lipids and cholesterol due to diet and life-style. The relationship between severe hyperlipidemia and thrombosis has been extensively investigated, but the effects of the preliminary stages of hyperlipidemia on platelet function are unclear. Therefore, we investigated how moderate elevation of different plasma lipid profiles influence platelet activation and thrombus formation, as compared to higher plasma lipid concentrations. Hyperlipidemic Apoe-/- and Ldlr-/- and wild-type mice were fed a normal chow diet, resulting in mildly increased plasma cholesterol. Blood from both knockout mice was used in comparison to wild-type mice, for multiparameter ex vivo measurements of thrombus formation under flow. Whole blood (fibrin-)thrombus formation on collagen in the absence or presence of coagulation (with(out) tissue factor), indicated enhancement of the thrombotic process in both knockout mice. These effects were not further aggravated in aged mice, as well as in Apoe-/- mice on high fat diet with very high plasma cholesterol levels. Bone marrow chimeras of wild-type or Ldlr-/- platelets into irradiated Ldlr-/- recipient mice showed similar thrombus formation patterns. This suggested that hyperlipidemia itself, not the platelet LDL receptor deficiency is responsible for the altered platelet activation status in Ldlr-/- mice. Exploration of the platelet proteome revealed high similarity between the three genotypes, although some proteins showed significantly changed expression in Apoe-/- mice. Finally, platelet lipidomic analysis showed an increased lipid profile in mildly hyperlipidemic mice, which may further contribute to the observed prothrombotic phenotype
2021-01-08 | PXD020276 | Pride
Project description:We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001). The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from whole blood samples. 40 Samples.
2014-08-09 | E-GEOD-31276 | biostudies-arrayexpress
Project description:We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001). The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled.
2014-08-09 | GSE31276 | GEO
Project description:Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The TALLYHO/JngJ (TH) mouse is a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. To determine the genetic factors that contribute to these T2D related characteristics in TH mice, we interbred TH mice with C57BL/6J (B6) mice. The parental, F1, and F2 mice were phenotyped at 8, 12, 16, 20, and 24 weeks of age for 4-hour fasting plasma triglyceride, cholesterol, insulin, and glucose levels, as well as body weights. Fat pad and carcass weights were measured at 24 weeks after sacrificing the mice. The F2 mice were genotyped genome-wide for 68 markers. Of 393 genotyped F2 mice, 16 were chosen from the extremes of the triglyceride distribution (8 high and 8 low), and liver, pancreas, muscle and adipose tissue were measured for gene expression. Gene expression quantitative trait locus (eQTL) analysis aided in selection of candidates underlying hyperlipidemia, diabetes and obesity QTLs. We identified several genetic loci that affected quantitative variation in plasma lipid and glucose levels and obesity traits.
2010-12-01 | GSE24637 | GEO