Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA139849 | ENA |
REPOSITORIES: ENA
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Project description:The impact of a dual TLR7 and TLR9 antagonist on hypercholesteremia and atherosclerosis was evaluated in hyperlipidemic mice. Treatment with antagonist induced a dose dependent reduction of total cholesterol (TC) and LDL-cholesterol. Changes in Adiponectin, Leptin and free fatty acids levels were observed. Plaque formation was inhibited in ApoE-/- and LDL-R-/- mice fed high fat diet and treated with the antagonist. Hepatic and renal steatosis was reduced by the treatment. Induction of IL-10 expression was inversely correlated with TC levels. The antagonist induced decrease in hepatic IKKα protein level and enhancement of Akt and Gsk3β phosphorylation. Treatment of C57BL/6 mice caused increase in hepatic LXR, PPARγ and ABCG1 expression and in stool content of TC. Antagonist treatment resulted in altered expression of several genes and pathways related to immune system, cholesterol, fatty acid and glucose metabolism. Data obtained suggest involvement of TLR7 and TLR9 in diet induced hyperlipidemia and atherosclerosis and demonstrate therapeutic potential of TLR7/9 antagonist.
2021-11-01 | GSE28125 | GEO
Project description:Trifluoroacetate Lowers Plasma Lipid Levels and Reduces the Development of Atherosclerosis in Mice
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Project description:Endothelial TGFβ signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFβ signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. We performed scRNAseq method to examine endothelial cell gene expression profile using Apoe and EC specific TGFbR1/2 KO in Apoe background mice.
2019-08-26 | GSE134557 | GEO
Project description:Endothelial TGFβ signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFβ signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. We performed scRNAseq method to examine endothelial cell gene expression profile using Apoe and EC specific TGFbR1/2 KO in Apoe background mice.
2019-08-26 | GSE134556 | GEO
Project description:Endothelial TGFβ signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFβ signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. We performed scRNAseq method to examine endothelial cell gene expression profile using Apoe and EC specific TGFbR1/2 KO in Apoe background mice.
2019-08-26 | GSE134555 | 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:MicroRNAs (miRNAs) are important regulators and potential therapeutic targets of metabolic disease. In this study we show by in vivo administration of locked nucleic acid (LNA) inhibitors that suppression of endogenous miR-29 lowers plasma cholesterol levels by ~40%, commensurate with the effect of statins, and reduces fatty acid content in the liver by ~20%. Whole transcriptome sequencing of the liver reveals 883 genes dysregulated (612 down, 271 up) by inhibition of miR-29. The set of 612 down-regulated genes are most significantly over-represented in lipid synthesis pathways. Among the up-regulated genes are the anti-lipogenic deacetylase sirtuin 1 (Sirt1) and the anti-lipogenic transcription factor aryl hydrocarbon receptor (Ahr), the latter of which we demonstrate is a direct target of miR-29. In vitro radiolabeled acetate incorporation assays confirm that pharmacologic inhibition of miR-29 significantly reduces de novo cholesterol and fatty acid synthesis. Our findings indicate that miR-29 controls hepatic lipogenic programs, likely in part through regulation of Ahr and Sirt1, and therefore may represent a candidate therapeutic target for metabolic disorders such as dyslipidemia. Hepatic mRNA profiles of C57BL/6J female mice treated with LNA against miR-29a, miR-29b and miR-29c versus saline.
2015-08-07 | E-GEOD-63493 | biostudies-arrayexpress
Project description:(Pro)renin receptor inhibition reduces plasma cholesterol and triglycerides but does not attenuate atherosclerosis in atherosclerotic mice
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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:Finasteride is commonly prescribed to treat benign prostate hyperplasia and male-pattern baldness in cis men and, more recently, trans individuals. However, the effect of finasteride on cardiovascular disease remains elusive. We evaluated the role of finasteride on atherosclerosis using low-density lipoprotein (LDL) receptor-deficient (Ldlr-/-) mice. Next, we examined the relevance to humans by analysing the data deposited between 2009 and 2016 in the National Health and Nutrition Examination Survey (NHANES). We show that finasteride reduces total plasma cholesterol and delays the development of atherosclerosis in Ldlr-/- mice. Finasteride reduced monocytosis, monocyte recruitment to the lesion, macrophage lesion content, and necrotic core area, the latter of which is an indicator of plaque vulnerability in humans. RNA sequencing analysis revealed a downregulation of inflammatory pathways and an upregulation of bile acid metabolism, oxidative phosphorylation, and cholesterol pathways in the liver of mice taking finasteride. Men reporting the use of finasteride showed lower plasma levels of cholesterol and LDL-cholesterol than those not taking the drug. Our data unveil finasteride as a potential treatment to delay cardiovascular disease in people by improving the plasma lipid profile.
2024-03-06 | GSE255708 | GEO