Murine Pulmonary Response to Chronic Hypoxia is Strain Specific
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE7823 | GEO | 2007/05/18
SECONDARY ACCESSION(S): PRJNA100057
REPOSITORIES: GEO
Similar Datasets
Project description:6-8 week old BL6, FVB/N and SV129 mouse strains were kept in normoxia or hypobaric hypoxia for 4 weeks and then phenotyped by echocardiogram and right ventricular heart catheterization, followed by tissue collection. In addition, Affymetrix expression analysis was conducted in a paired fashion. Experiment Overall Design: This series actually includes another 12 arrays. However, the others had technical difficulties and so aren't really appropriate for general distribution.
2008-06-15 | E-GEOD-7823 | biostudies-arrayexpress
Project description:Right ventricular (RV) failure is the major determinant of outcome in pulmonary hypertension (PH). Calves exposed to 2-wks environmental hypoxia develop severe PH and unlike rodents, chronic hypoxia-induced PH in this species can lead to right heart failure. We therefore sought to examine the molecular and structural changes in the RV in calves with hypoxia-induced PH, hypothesizing that we could identify mechanisms underlying compensated physiological function in the face of developing severe PH. Calves were exposed to 14d of hypobaric hypoxia (PB=430 mm Hg, equivalent to 4570m elevation, n=29) or ambient normoxia (1525m, n=25). Cardiopulmonary function was evaluated by right heart catheterization and pressure volume loops. Molecular and cellular determinants of RV remodeling were analyzed by cDNA microarrays, RealTime PCR, proteomics and immunochemistry. Hypoxic exposure induced robust PH, with increased RV contractile performance and preserved cardiac output, yet evidence of dysregulated RV-pulmonary artery mechanical coupling consistent with advanced PH. Analysis of gene expression revealed cellular processes associated with structural remodeling, cell signaling, and survival. We further identified specific clusters of gene expression associated with (i) hypertrophic gene expression and pro-survival mechanotransduction through YAP-TAZ signaling, (ii) ECM remodeling, (iii) inflammatory cell activation and (iv) angiogenesis. A potential transcriptomic signature of cardiac fibroblasts in RV remodeling was detected. Proteomic and immunohistochemical analysis confirmed RV myocyte hypertrophy, together with localization of ECM remodeling, inflammatory cell activation, and endothelial cell proliferation within the RV interstitium. In conclusion, hypoxia and hemodynamic load initiate coordinated processes of protective and compensatory RV remodeling to withstand the progression of PH.
2023-03-20 | GSE217438 | GEO
Project description:For individuals migrating to or residing permanently at high-altitude regions, environmental hypobaric hypoxia is a primary challenge which induces several physiological or pathological responses. It is well documented that human beings adapt to hypobaric hypoxia via some protective mechanisms, such as erythropoiesis and overproduction of hemoglobin, however little is known on the changes of plasma proteome profiles in accommodation to high-altitude hypobaric hypoxia. In the present study, we investigated differential plasma proteomes of high altitude natives and lowland normal controls by a TMT-based proteomic approach. A total of 818 proteins were identified, of which 137 were differentially altered. Bioinformatics (including GO, KEGG, protein-protein interactions, etc.) analysis revealed the dysregulated proteins were primarily involved in complement and coagulation cascades, anti-oxidative stress and glycolysis. Validations via magnetic Luminex® Assays and ELISA demonstrated that CCL18, C9, PF4, MPO and S100A9 notably up-regulated, and HRG and F11 down-regulated in high altitude natives compared with lowland controls, which were consistent with the proteomic results. Our findings highlight the roles of complement and coagulation cascades, anti-oxidative stress and glycolysis in acclimatization to hypobaric hypoxia and provide a foundation for developing potential diagnostic or/and therapeutic biomarkers for high altitude hypobaric hypoxia-induced diseases.
2019-03-27 | PXD012221 | Pride
Project description:To determine hypoxia mediated changes in whole blood, normal swiss webster mice were gradually exposed to a chronic hypobaric hypoxic environment up to 8500m, for 2 weeks in vivo. Control, age-matched mice were maintained under normoxic conditions in Kathmandu (c. 1300 mts above sea level). Purpose: To examine and characterize the expression profile of genes expressed at hypobaric hypoxia on Mt. Everest of whole blood in comparison to the control. Methods: At the beginning of the experiment mice were divided into two groups, control (room condition, Kathmandu, Nepal) and hypoxic (hypoxic condition). For conditioning, the hypoxic group was exposed to lower levels of hypobaric hypoxia during our mountaineering expedition to Mt Everest. The oxygen level was decreased according to our climbing protocol from 21% to about 7% over a period of 15 days. Food and water were changed daily during the course of the experiment. After 15 days animals were euthanized after whole blood extraction from V. Cava for further analysis. RNA from whole blood was isolated, processed and used for microarray-based expression profiling. Profiles were generated for genes differentially expressed at control versus hypobaric hypoxia in whole blood using a false discovery rate (FDR) of 0%.We validated the profiles by real-time quantitative reverse transcription-polymerase chain reaction (qPCR). Results: The regional transcriptomes associated with hypobaric hypoxia on Mt. Everest in whole blood were identified. We found 947 genes that were differentially expressed in normobaric hypoxic whole blood compared to control with a 0% FDR and a 2 fold cutoff. Conclusion: Transcriptome level differences exist between control and hypobaric hypoxia in whole blood. Our definition of the synaptic transcriptome provides insight into the functioning of the unique response to hypoxia in whole blood.
2010-05-07 | E-GEOD-15901 | biostudies-arrayexpress
Project description:Pulmonary hypertension (PH), a rare disorder is a complication of a number of cardiopulmonary, unrelated systemic diseases, drug toxicity and genetic mutations. Major advances have been made in the field, but the pathogenesis of PH is not yet understood. Several experimental models such as monocrotaline (MCT) and hypoxia have been used to understand the mechanism underlying the pathogenesis of PH. We have recently shown that that the addition of hypoxia to MCT injected rats accelerates the disease process leading to neointima formation. We have profiled the lungs of adult male Sprague-Dawley rats kept for 4 weeks in normal atmospheric conditions or in hypobaric hypoxia (380 mmHg) w/o subcutaneous injection with 40 mg/kg MCT or just saline. While MCT and hypoxia altered expression of few genes when applied separately, together they induced a substantial alteration of the transcriptome. The most profoundly altered pathways by the combined effect of hypoxia and MCT were: endocytosis, apoptosis, HIF-1 signaling pathway and vascular smooth muscle contraction. Two-condition (C = normal atmospheric conditions (control) vs H = hypobaric hypoxia) + two treatment (M = with MCT, O = without MCT) experiment. Four biological replicas of each combination: CO, HO, CM, HM. Differently labeled biological replicates were cohybridized with each array. Results of similarly labeled different conditions were compared then averaged for the two fluorescent labels. For instance: CO1 & CO3 were compared with CM1 & CM3, CO2 & CO4 were compared with CM2 & + CM4, and the results of the comparisons averaged. This design uses 100% of the resources, has a better normlaiztion and allows all possible comparisons among the conditions.
2015-09-04 | E-GEOD-72707 | biostudies-arrayexpress
Project description:Hypobaric Hypoxia Induced Transcriptional profiling of Bovine (Bos indicus)
2010-09-20 | E-MEXP-2118 | biostudies-arrayexpress
Project description:Aim: Acute hypobaric hypoxia occurs during fast ascent and brief sojourns to high altitudes. We aimed to elucidate early phase molecular mechanisms during hypobaric hypoxia that may contribute towards differential physiological responses in susceptible and tolerant rats. Methods: Sprague-Dawley rats representing susceptible, normal (moderate) and tolerant male and female groups were subjected to simulated acute hypobaric hypoxia for one hour at 9144 m and 24°C. The lung tissue samples were subjected to high throughput mRNA-seq based transcriptome profiling. Differential gene expression of selected genes was validated by qRT-PCR. Results: The cellular mechanisms found to be playing significant role in hypobaric hypoxia included MAPK, p53 and JAK-STAT signaling, and hypometabolism. Upregulated expression of early response genes including Dusp1, Cdkn1a, Txnip, Rgs1 and Rgs2 in susceptible rats indicated a progression towards growth arrest and apoptosis, while elevated expression of cell adhesion molecules, wound healing and repair bioprocesses was found in tolerant males. Upregulated Kcnj15 and Vsig4 variants in tolerant females suggested hypoxia adaptation by fluid reabsorption to avoid edematous conditions and suppression of T cell proliferation to avoid acute lung inflammation. Conclusion: The differential gene expression patterns in different experimental sets elucidated the physiological mechanisms associated with progressive damage in the lung tissues of susceptible and normal (moderate) rats, and tissue protective measures in tolerant rats during acute hypobaric hypoxia.
2018-07-01 | GSE62688 | GEO
Project description:In this work we have described the protein nitration profile in the brain of rats submitted to an experimental model of hypobaric hypoxia
2014-07-30 | PXD001049 | Pride
Project description:Pulmonary hypertension (PH), a rare disorder is a complication of a number of cardiopulmonary, unrelated systemic diseases, drug toxicity and genetic mutations. Major advances have been made in the field, but the pathogenesis of PH is not yet understood. Several experimental models such as monocrotaline (MCT) and hypoxia have been used to understand the mechanism underlying the pathogenesis of PH. We have recently shown that that the addition of hypoxia to MCT injected rats accelerates the disease process leading to neointima formation. We have profiled the lungs of adult male Sprague-Dawley rats kept for 4 weeks in normal atmospheric conditions or in hypobaric hypoxia (380 mmHg) w/o subcutaneous injection with 40 mg/kg MCT or just saline. While MCT and hypoxia altered expression of few genes when applied separately, together they induced a substantial alteration of the transcriptome. The most profoundly altered pathways by the combined effect of hypoxia and MCT were: endocytosis, apoptosis, HIF-1 signaling pathway and vascular smooth muscle contraction.
2015-09-04 | GSE72707 | GEO
Project description:The aim of this experiment was to evaluate the changes in gene expression in response to hypoxia and/or cisplatin in an ovarian cancer cell line model. A2780 (cisplatin-sensitive) and A2780cis (cisplatin-resistant) cell lines were treated with cisplatin in normoxia or hypoxia (0.5% O2) for 72 hours. RNA was extracted from three independent biological replicates for each condition: A2780 (normoxia, untreated); A2780 (hypoxia, untreated); A2780 (normoxia, cisplatin); A2780cis (hypoxia, cisplatin), A2780cis (normoxia, untreated); A2780cis (hypoxia, untreated); A2780cis (normoxia, cisplatin); A2780cis (hypoxia, cisplatin) and interrogated on Affymetrix Human Gene ST 1.0 arrays.
2016-01-15 | E-MTAB-3645 | biostudies-arrayexpress