Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205050 | GEO | 2022/09/05
REPOSITORIES: GEO
Similar Datasets
Project description:Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells
| PRJNA843452 | ENA
Project description:Endothelial cell (EC) dysfunction precedes the development of cardiovascular disease in OSA; however, the mechanisms by which ECs respond to these hypoxic events is poorly understood. To better understand EC responses to hypoxia, we examined the effects of both sustained hypoxia (SH) and intermittent hypoxia (IH) on the activation of HIF-1α in Endothelial Cells (ECs). While SH stabilized HIF-1α and led to its nuclear localization, IH didn’t activate HIF-1α and its downsteram gene expression. Using RNA-sequencing, we evaluated transcriptional responses of ECs to hypoxia. SH induced expression of HIF-1α and hypoxia response genes, while IH affected cell-cycle regulation genes.
2024-11-01 | GSE279434 | GEO
Project description:Intermittent hypoxia (IH) in HeLa cell culture activates proinflammatory transcription factor NFκB, whereas chronic hypoxia (CH) does not. In order to determine whether IH may be linked to vascular inflammation, we developed a novel IH cell culture system and exposed HAEC (human aortic endothelial cells) to IH or CH. Keywords: Human Artery Endothelial Cells (HAEC)
2008-12-31 | GSE10723 | GEO
Project description:Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular disease. While intermittent hypoxia (IH) and catecholamine release play an important role in this increased risk, the mechanisms are incompletely understood. We have recently reported that IH causes endothelial cell (EC) activation, an early phenomenon in the development of cardiovascular disease, via IH-induced catecholamine release. Here, we investigated the effects of IH and epinephrine on gene expression in human aortic ECs using RNA-sequencing. We found a significant overlap between IH and epinephrine-induced differentially expressed genes (DEGs) including enrichment in leukocyte migration, cytokine-cytokine receptor interaction, cell adhesion and angiogenesis. Epinephrine caused higher number of DEGs compared to IH. Interestingly, IH when combined with epinephrine had an inhibitory effect on epinephrine-induced gene expression. Combination of IH and epinephrine induced MT1G (Metallothionein 1G), which has been shown to be highly expressed in ECs from parts of aorta (i.e., aortic arch) where atherosclerosis is more likely to occur. In conclusion, epinephrine has a greater effect than IH on EC gene expression in terms of number of genes and their expression level. IH inhibited the epinephrine-induced transcriptional response. Further investigation of the interaction between IH and epinephrine is needed to better understand how OSA causes cardiovascular disease.
| S-EPMC9561121 | biostudies-literature
Project description:Study objectives: Chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome is associated with excess mortality, and outcomes are related to the degree of hypoxemia. People at high altitude are susceptible to periodic breathing, and hypoxia at altitude is associated with cardio-metabolic dysfunction. Hypoxemia in these scenarios may be described as superimposed sustained plus intermittent hypoxia, or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice. Methods: C57BL/6J mice were subjected to either sustained hypoxia (SH, FiO2=0.10), intermittent hypoxia (IH, FiO2=0.21 for 12 hours, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 hours), OH (FiO2=0.13 for 12 hours, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 hours), or room air (RA), n=8/group. Blood pressure and intraperitoneal glucose tolerance test were measured serially, and right ventricular systolic pressure (RVSP) was assessed. Results: Systolic blood pressure transiently increased in IH and OH relative to SH and RA. RVSP did not increase in IH, but increased in SH and OH by 52% (p<0.001) and 20% (p=0.001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum LDL and VLDL increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH. Conclusions: Overlap hypoxia may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of sustained hypoxia.
2021-12-01 | GSE189958 | GEO
Project description:Obstructive sleep apnea (OSA) leads to increased cardiovascular morbidity and mortality, which have been attributed to intermittent hypoxia (IH). The effects of IH on lung structure and function are unknown. We used a mouse model of chronic IH, which mimics the O2 profile in patients with OSA. We exposed adult C57BL/6J mice to 3 months of IH with an FIO2 nadir of 5%, 60 times/hr during the 12hr light phase. Control mice were exposed to room air. Gene microarrays were performed in a separate subset of animals (IH, n = 5; control, n = 5). Total RNA was isolated from lung tissue using the Trizol Reagent method, gene microarrays were performed with the Affymetrix GeneChip® Mouse Genome 430A 2.0 Array (MG 430A 2.0; Affymetrix, Inc., Santa Clara, CA) and analyzed using Significance Analysis of Microarray (SAM) software.
2010-12-31 | E-GEOD-21409 | biostudies-arrayexpress
Project description:Obstructive sleep apnea (OSA) leads to increased cardiovascular morbidity and mortality, which have been attributed to intermittent hypoxia (IH). The effects of IH on lung structure and function are unknown. We used a mouse model of chronic IH, which mimics the O2 profile in patients with OSA. We exposed adult C57BL/6J mice to 3 months of IH with an FIO2 nadir of 5%, 60 times/hr during the 12hr light phase. Control mice were exposed to room air.
2010-12-31 | GSE21409 | GEO
Project description:Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which has been proposed as the major determinant of processes involving tumor invasion and metastasis. To study whether circulating DNA (cirDNA) in blood plasma reflects the changes that the tumor cells undergo under IH conditions, we used a xenografted murine model. Mice engrafted with TC1 epithelial lung and controls were exposed to IH or room air (RA) conditions. Plasma cirDNA amounts were significantly increased in mice exposed to IH (p<0.05). We found a significant correlation between plasma cirDNA concentration and tumor size, weight and invasiveness (p<0.05). Using a microarray-based approach, we identified 2,094 regions showing significant differential cirDNA modifications. System biology analysis revealed an association with molecular pathways misregulated in cancer progression and with distal and TSS-associated transcription factor binding sites. We detected clusters of highly variable regions in chromosomes 7, 13, 14 and X, which may highlight hotspots for DNA deletions. Single locus displayed high intragroup variation, suggesting cellular heterogeneity within the tissue may be associated to cirDNA release. Our result showed that exposure to IH increases the shedding of cirDNA into circulation, which carries epigenetic modifications that may characterize cell populations within the tumor that preferentially release their DNA upon IH exposure. 6 xenografted mouse samples were analyzed by microarray analysis: Mouse exposed to IH (n=3, XenoIH group) and mouse exposed to room air conditions (n=3, XenoRA group)
2015-02-24 | E-GEOD-61070 | biostudies-arrayexpress
Project description:Background: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O2) intermittent or constant hypoxia. Methodology/Principal Findings: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. Conclusions/Significance: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival. Expression profiles were determined by expression arrays in Drosophila melanogaster following acute constant or intermittent hypoxia. Three groups of samples were included in this analysis (3 x control, 3x CH treated and 3 x IH treated samples).
2009-04-30 | E-GEOD-14981 | biostudies-arrayexpress
Project description:Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which has been proposed as the major determinant of processes involving tumor invasion and metastasis. To study whether circulating DNA (cirDNA) in blood plasma reflects the changes that the tumor cells undergo under IH conditions, we used a xenografted murine model. Mice engrafted with TC1 epithelial lung and controls were exposed to IH or room air (RA) conditions. Plasma cirDNA amounts were significantly increased in mice exposed to IH (p<0.05). We found a significant correlation between plasma cirDNA concentration and tumor size, weight and invasiveness (p<0.05). Using a microarray-based approach, we identified 2,094 regions showing significant differential cirDNA modifications. System biology analysis revealed an association with molecular pathways misregulated in cancer progression and with distal and TSS-associated transcription factor binding sites. We detected clusters of highly variable regions in chromosomes 7, 13, 14 and X, which may highlight hotspots for DNA deletions. Single locus displayed high intragroup variation, suggesting cellular heterogeneity within the tissue may be associated to cirDNA release. Our result showed that exposure to IH increases the shedding of cirDNA into circulation, which carries epigenetic modifications that may characterize cell populations within the tumor that preferentially release their DNA upon IH exposure.
2015-02-24 | GSE61070 | GEO