Gene expression and phenotypic characterization of mouse heart after chronic constant or intermittent hypoxia
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ABSTRACT: Chronic constant hypoxia (CCH), such as in pulmonary diseases or high altitude, and chronic intermittent hypoxia (CIH), such as in sleep apnea, can lead to major changes in the heart. The molecular mechanisms underlying these cardiac alterations are not well understood. We hypothesized that analysis on the changes in gene expression could help to delineate such mechanisms. In addition, the differences that can be anticipated between CCH and CIH could be potentially dissected. Current study used CCH and CIH mouse models combined with cDNA microarrays to determine the changes of gene expression in CCH or CIH mice heart. Keywords = heart Keywords = hypoxia Keywords = mouse Keywords = microarray Keywords: time-course
Project description:Chronic constant hypoxia (CCH), such as in pulmonary diseases or high altitude, and chronic intermittent hypoxia (CIH), such as in sleep apnea, can lead to major changes in the heart. The molecular mechanisms underlying these cardiac alterations are not well understood. We hypothesized that analysis on the changes in gene expression could help to delineate such mechanisms. In addition, the differences that can be anticipated between CCH and CIH could be potentially dissected. Current study used CCH and CIH mouse models combined with cDNA microarrays to determine the changes of gene expression in CCH or CIH mice heart. Keywords = heart Keywords = hypoxia Keywords = mouse Keywords = microarray Keywords: time-course
Project description:In this study, we determined the effect of chronic consistent hypoxia (CCH) and chronic intermittent hypoxia (CIH) on global gene expression in cortical and hippocampal region of developing mouse brain using long-oligo beadschip arrays. Keywords: Gene expression profile Control-Cortex: Cortical samples from 16 days old mice were analysed on whole-genome expression chips to reveal expression profile at this developmental stage. Used as control for Chronic Hypoxia Treated cortical samples. CCH-Cortex: Cortical samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression profile following 2-week CCH treatment. CIH-Cortex: Cortical samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression profile following 2-week CIH treatment. Control-Hippocampus: Hippocampal samples from 16 days old mice were analysed on whole-genome expression chips to reveal expression profile at this developmental stage. Used as control for Chronic Hypoxia Treated hippocampal samples. CCH-Hippocampus: Hippocampal samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression following 2-week CCH treatment. CIH-Hippocampus: Hippocampal samples from 2-week CCH treated mice were analysed on whole-genome expression chips to reveal the changes in gene expression following 2-week CIH treatment.
Project description:In this study, we determined the effect of chronic consistent hypoxia (CCH) and chronic intermittent hypoxia (CIH) on global gene expression in cortical and hippocampal region of developing mouse brain using long-oligo beadschip arrays. Keywords: Gene expression profile
Project description:Transcriptomic studies were undertaken to investigate the effect of hypoxia on kidney in early life to elucidate the genomic basis of renal injury and adaptation when oxygen is deprived. Fluorescently labeled, reverse-transcribed kidney RNA from 18 male and 18 female P2 mice, subjected for one, two or four weeks to normal atmospheric conditions (NAC) or to chronic constant (CCH) or intermittent (CIH) hypoxia were hybridized with 18 cDNA microarrays ("multiple yellow strategy", MYS). Expression level, stability, coordination and maturation of 1775 distinct genes were studied in each treatment-duration condition. Results: Both CIH and CCH change the expression level, stability and coordination of numerous genes that are involved in most major functional pathways. The fold change was significantly higher in female mice after one week of hypoxia and significantly higher in males after two and four weeks of hypoxia. Most solute carrier genes, including NHE1, are up-regulated and few down-regulated. There are genes coordinately expressed but others are much less so, with a remarkable overlap between the genes that are coexpressed in NAC and coregulated in CCH and CIH. Conclusion. Hypoxia is a major stress that alters the profile, stability and coordination of the kidney transcriptome in early life and slows down its maturation. Keywords: stress response
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.
Project description:Neovascular retinopathies and edema are sign threatening complications of ischemic retinopathies, such as retinopathy of prematurity (ROP) and diabetic retinopathy (DR). Sleep apnea that leads to chronic intermittent hypoxia (CIH) is an independent risk factor for severe disease, but the underlying mechanisms are unknown. Here we show that experimental CIH during the ischemic phase of oxygen induced retinopathy in mice severely reduces beneficial revascularitzation of the ischemic retina, and increases neuronal loss and pathological neovascularization. Mechanistically we demonstrate that CIH reduces both colony stimulation factor 1 (CSF-1) expression and the ischemia-induced increase of retinal microglial cells that promotes the revascularization of the ischemic retina in the absence of CIH. Local CSF1R inhibition during ischemic retinopathy reduced the number of microglial cells, inhibited revascularization, and exacerbated pathological neovascularization, recapitulating several effects of CIH. Our findings provide a novel mechanism by which sleep apnea and CIH aggravate ischemic retinopathies, underscoring the importance of treating apnea in ROP and DR to help prevent sight threatening severe disease.
Project description:Obstructive sleep apnea (OSA) syndrome is characterized by Chronic Intermittent Hypoxia (CIH). In this study, we employed Data-independent acquisition (DIA) Mass Spectrometry to conduct comprehensive proteomic and phosphoproteomic profiling of a murine model subjected to Chronic Intermittent Hypoxia (CIH), a model we had previously established. Utilizing three CIH and three normal control genioglossus samples, we gathered valuable insights into the molecular alterations associated with CIH.
Project description:Gene expression profile of the response to chronic constant hypoxia in the heart of adult zebrafish Experiment Overall Design: 10 arrays (5 for hypoxia and 5 normoxia); in total 8 biological samples plus 2 technical replicates
Project description:Background: Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. Methods: To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–tandem mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 4 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Results: Our analysis identified and quantified 2699 lysine acetylation sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant downregulation of proteins that are known to be involved in endocrine hormone secretion. Metabolomic analysis of plasma suggested significant alterations in glycerophospholipid and amino acids metabolism, neuroactive ligand-receptor interaction and serotonergic synapse in children with OSA; these changes may represent potential mechanisms underlying the pathogenesis of OSA in children. Conclusion: This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus, as well as its potential role in endocrine impairment.
Project description:Gene expression profile of the response to chronic constant hypoxia in the heart of adult zebrafish Keywords: Adaptive response to chronic constant hypoxia in the heart