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ABSTRACT:
PROVIDER: PRJNA1063660 | ENA |
REPOSITORIES: ENA
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Project description:Alternate high fat diet aggravates atherosclerosis through an IL1b-dependent reprogramming of neutrophil progenitors
| PRJNA1061499 | ENA
Project description:Alternate high fat diet aggravates atherosclerosis through an IL1B- 2 dependent reprogramming of neutrophil progenitors
| PRJNA1068574 | ENA
Project description:Systemic immune responses induced by chronic hypercholesterolemia contribute to the initiation, progression and complications of atherosclerosis. However, the consequences of an alternate high fat diet and the associated variations in plasma cholesterol levels on atherosclerosis are unknown. To address this relevant issue concerning common situations where dietary habits change over time, we developed a novel protocol in athero-prone mice that allowed us to compare the effects of alternate versus continuous high fat diet (HFD) on atherosclerosis, the overall period of time of exposure to HFD being similar between groups. We showed that alternate HFD lead to accelerated atherosclerosis in Ldlr-/- and Apoe-/- mice compared to continuous HFD. The pro-atherogenic effect of alternate HFD was also found in Apoe-/-Rag2-/- mice lacking T, B, and NKT cells, ruling out a role for the adaptive immune system in the observed phenotype. Using different complementary in vivo approaches, we found that lipid-rich diet discontinuation in alternate group downregulated Runx1, a negative regulator downstream of TLR-4 pathways. As a result, after re-exposure to HFD, myeloid progenitors were more sensitive to hypercholesterolemia leading to acute differentiation into IL-1b- producing immature neutrophils, which caused a state of emergency myelopoiesis. Consecutively, neutrophils markedly increased in the peripheral blood, infiltrated atherosclerotic lesions and locally released neutrophil extracellular traps. Anti-Ly6G neutrophil depletion abolished the pro-atherogenic effects of alternate HFD. Specific deletion of Il1b and Il1b receptor confirmed that the IL-1b signaling pathway was a major driver of the pro-inflammatory and pro-atherogenic neutrophil signature. Finally, treatment with anti-IL-1b neutralizing antibody or inflammasome inhibitor during re-exposure to HFD reversed the pro-atherogenic effects of alternate HFD. In summary, we showed that alternate HFD accelerates atherosclerosis through IL-1b-dependent neutrophil progenitor reprogramming.
2024-04-14 | GSE252604 | GEO
Project description:Systemic immune responses induced by chronic hypercholesterolemia contribute to the initiation, progression and complications of atherosclerosis. However, it is common for individuals to change dietary habits over time. The consequences of an alternating high fat diet and the associated variations in plasma cholesterol levels on atherosclerosis are unknown. To address this relevant issue, we developed a novel protocol in atherosclerosis-prone mice that allowed us to compare the effects of alternate versus continuous high fat diet (HFD) on atherosclerosis, while keeping the overall period of exposure to HFD similar between groups. We showed that an alternate HFD lead to accelerated atherosclerosis in Ldlr-/- and Apoe 55 -/- mice compared to continuous HFD. This pro-atherogenic effect of alternate HFD was also observed in Apoe-/-Rag2 57 -/- mice lacking T, B, and NKT cells, ruling out the role of the adaptive immune system in the observed phenotype. Employing various complementary in vivo approaches, we discovered that discontinuing HFD in the alternate group downregulated Runx1, a negative regulator of inflammatory signaling pathways in the myeloid lineage. Consequently, after re61 exposure to HFD, myeloid progenitors were primed to respond to HFD re-exposure by differentiating into IL-1-producing immature neutrophils, and inducing a state of emergency myelopoiesis. Subsequently, neutrophils markedly increased in the peripheral blood, infiltrated atherosclerotic lesions and locally released neutrophil extracellular traps. Anti-Ly6G neutrophil depletion abolished the pro-atherogenic effects of alternate HFD. Specific deletion of Il1b and Il1 receptor confirmed that the IL-1 signaling pathway was a major driver of the pro67 inflammatory and pro-atherogenic neutrophil signature. Finally, treatment with anti-IL-1 neutralizing antibody or an inflammasome inhibitor during re-exposure to HFD reversed the pro-atherogenic effects of alternate HFD. In summary, we showed that alternate HFD accelerates atherosclerosis through IL-1-dependent neutrophil progenitor reprogramming.
2024-04-23 | GSE254105 | GEO
Project description:Atherosclerosis is the pathological basis of cardiovascular disease. Obstructive sleep apnea aggravates atherosclerosis, and chronic intermittent hypoxia (CIH) as a prominent feature of obstructive sleep apnea plays an important role during the process of atherosclerosis. The mechanisms of CIH in the development of atherosclerosis remain unclear. The microarray was used to investigate differentially expressed mRNAs and long noncoding RNAs (lncRNAs) in aorta from five groups of ApoE-/- mice fed with a high-fat diet and exposed to various conditions: normoxia for 8 weeks, CIH for 8 weeks, normoxia for 12 weeks, CIH for 12 weeks, or CIH for 8 weeks followed by normoxia for 4 weeks.
2020-02-14 | GSE145221 | GEO
Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver
2007-11-01 | E-GEOD-363 | biostudies-arrayexpress
Project description:The long-term impact of systemic hypoxia resulting from Acute Respiratory Distress Syndrome (ARDS) on the function of short-lived innate immune cells is unclear. We show that patients 3-6 months after recovering from ARDS have persistently impaired circulating neutrophil effector functions and an increased susceptibility to secondary infections. These defects are linked to a widespread loss of the activating histone mark H3K4me3 in genes crucial for neutrophil activities. By studying healthy volunteers exposed to altitude-induced hypoxemia, we demonstrate that oxygen deprivation alone causes this long-term neutrophil reprogramming. Mechanistically, mouse models of systemic hypoxia reveal that persistent loss of H3K4me3 originates in proNeu and preNeu progenitors within the bone marrow and is linked to N-terminal histone 3 clipping, which removes the lysine residue for methylation. Thus, we present novel evidence that systemic hypoxia initiates a sustained maladaptive reprogramming of neutrophil immunity by triggering histone 3 clipping and H3K4me3 loss in neutrophil progenitors.
2025-09-22 | PXD065461 | Pride
Project description:The long-term impact of systemic hypoxia resulting from Acute Respiratory Distress Syndrome (ARDS) on the function of short-lived innate immune cells is unclear. We show that patients 3-6 months after recovering from ARDS have persistently impaired circulating neutrophil effector functions and an increased susceptibility to secondary infections. These defects are linked to a widespread loss of the activating histone mark H3K4me3 in genes crucial for neutrophil activities. By studying healthy volunteers exposed to altitude-induced hypoxemia, we demonstrate that oxygen deprivation alone causes this long-term neutrophil reprogramming. Mechanistically, mouse models of systemic hypoxia reveal that persistent loss of H3K4me3 originates in proNeu and preNeu progenitors within the bone marrow and is linked to N-terminal histone 3 clipping, which removes the lysine residue for methylation. Thus, we present novel evidence that systemic hypoxia initiates a sustained maladaptive reprogramming of neutrophil immunity by triggering histone 3 clipping and H3K4me3 loss in neutrophil progenitors.
2025-09-22 | PXD065519 | Pride
Project description:The macrophage subpopulations that have therapeutic benefits against atherosclerosis have not yet been fully understood. A single-cell RNA sequencing analysis were performed on the F4/80+ macrophages of apolipoprotein E-deficient (Apoe−/−) mice on a normal diet (ND), a high-fat diet (HFD), and a high-fat diet (HFD) with anti-CVI-mAb treatment. We analyze the diversity of M2 macrophages in atherosclerosis using single cell RNA sequencing (scRNA-seq).
2023-12-15 | GSE215103 | GEO
Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver Keywords: repeat sample
2003-04-05 | GSE363 | GEO