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Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype

ABSTRACT: Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype

PROVIDER: PRJNA785258 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17085575_1.fastq.gz	Fastqsanger.gz
	SRR17085575_2.fastq.gz	Fastqsanger.gz
	SRR17085576_1.fastq.gz	Fastqsanger.gz
	SRR17085576_2.fastq.gz	Fastqsanger.gz
	SRR17085577_1.fastq.gz	Fastqsanger.gz

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Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype

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

Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype.

Project description:Study objectivesChronic 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 altitudes 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 hypoxia (SH) plus intermittent hypoxia (IH), or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice.MethodsC57BL/6J mice were subjected to either SH (FiO2 = 0.10), IH (FiO2 = 0.21 for 12 h, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 h), OH (FiO2 = 0.13 for 12 h, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 h), 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.ResultsSystolic 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 < .001) and 20% (p = .001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum low- and very-low-density lipoproteins increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH.ConclusionsOH may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of SH.

| S-EPMC9189937 | biostudies-literature

Temporal effects of intermittent- and sustained hypoxia on gene expression patterns in rat lungs

Project description:Time-course gene expression profiles were obtained from lung tissues of the rats treated with room air, intermittent- (IH) or sustained hypoxia (SH) for 1, 3, 7, 14 and 30 days using CodeLink microarrays. Using a systems biology approach, we observed that two different mechanisms are involved in the lung responses to IH and SH: IH leads to increased G-protein coupled signaling-, ion transport-, neuronal- and steroid hormone receptor activities; whereas SH causes increased blood vessel morphogenesis and immune responses. Our results provide insight into molecular mechanisms underlying IH and SH. Keywords: gene expression array-based, count rats were treated with intermittent- (IH) or sustained hypoxia (SH) for 1, 3, 7, 14 and 30 days; rats treated with room air were used as controls; gene expression profiles were obtained from these rats

2008-12-17 | E-GEOD-8705 | biostudies-arrayexpress

Sustained and intermittent hypoxia differentially modulate primary monocyte immunothrombotic responses to IL-1b stimulation

Project description:We replicated the intricate conditions of the venous valve pocket using a state-of-the-art hypoxia chamber with software-controlled oxygen cycling. We comprehensively studied the effects of sustained and intermitted hypoxia alone or in combination with IL-1b to mimic VTE-associated inflammatory stimuli on primary monocytes. Our transcriptome analysis revealed that sustained hypoxia limited the pro-inflammatory response induced by IL-1b, and triggered a metabolic shift in the monocyte transcriptome. On the other hand, intermittent hypoxia alone had a modest effect, but in combination with IL-1b it significant altered the expression of 2207 genes. Notably, intermittent hypoxia enhanced the IL-1b -stimulatory effects on several chemokine and interleukin genes (e.g., IL-19, IL-24, IL-32, MIF), as well as genes involved in coagulation (thrombomodulin) and fibrinolysis (VEGFA, MMP9, MMP14 and PAI-1. The RNA seq data are paired with validations on protein level in the published paper. Our findings provide valuable insights into how the different hypoxic profiles shape the immunothrombotic response of monocytes and shed new light on the early events in the pathogenesis of venous thrombosis.

2023-06-15 | GSE234701 | GEO

Temporal effects of intermittent- and sustained hypoxia on gene expression patterns in rat lungs

2008-12-18 | GSE8705 | GEO

Intermittent and sustained hypoxia exposures activate distinct transcriptional responses in human aortic endothelial cells

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

Sustained and intermittent hypoxia combined with TNF additively promote pro-thrombotic gene and protein changes in primary endothelial cells.

Project description:Venous thromboembolism (VTE) is a common and deadly disease with unclear pathophysiological initiation. Hypoxia and inflammation are believed to contribute to promoting thrombosis, but how and if these potential triggers interact is unclear. We have stimulated primary endothelial cells with sustained and intermittent hypoxia, in the presence or absence of TNF. Effects to the cells were analyzed with RNA sequencing and flow cytometry after 24H and 48H stimulations. RNA sequencing confirmed strong pro-inflammatory effects of TNF, and indicated that hypoxia alone had modest effects, but when combined with TNF there were clear additive effects on the number of differentially expressed genes, as well as modest increases of pro-inflammatory GO terms assessed by GSEA. On protein level, flow cytometry confirmed additive effects of combingin hypoxia and TNF for several adhesion molecules including E-selectin and ICAM-1, as well as on associated molecules including tissue factor. Unsupervised clustering of the flow cytometric data also revealed the expansion of a subset of endothelial cells with strongly pro-thrombotic phenotype. Taken together, our data suggests that hypoxia combines with inflammatory cues in the in vivo situation to promote pro-thrombotic responses by endothelial cells in the venous valve pocket.

2023-09-17 | GSE243023 | GEO

Intermittent Hypoxia ageing

Project description:Expression data from mice exposed to intermittent hypoxia and mice reared for 12 months. We used microarrays to analyze the transcriptome of hippocampus from mice exposed to intermittent hypoxia or aged mice.

2016-12-27 | GSE62385 | GEO

Intermittent Hypoxia ageing

Project description:Intermittent Hypoxia ageing

| PRJNA263964 | ENA

Sustained and intermittent hypoxia differentially modulate primary monocyte immunothrombotic responses to IL-1b stimulation

Project description:Sustained and intermittent hypoxia differentially modulate primary monocyte immunothrombotic responses to IL-1b stimulation

| PRJNA982787 | ENA