Transcriptomic Modifications in Developmental Cardiopulmonary Adaptations to Chronic Hypoxia Using a Murine Model of Simulated High Altitude Exposure
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ABSTRACT:
PROVIDER: PRJNA588427 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10423200.fastq.gz | Fastqsanger.gz | |||
| SRR10423200_1.fastq.gz | Fastqsanger.gz | |||
| SRR10423200_2.fastq.gz | Fastqsanger.gz | |||
| SRR10423201.fastq.gz | Fastqsanger.gz | |||
| SRR10423201_1.fastq.gz | Fastqsanger.gz |
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Project description:Mechanisms driving adaptive developmental responses to chronic high altitude (HA) exposure are incompletely known. We developed a novel rat model mimicking the human condition of cardiopulmonary adaptation to HA starting at conception and spanning the in utero and early life timeframe. We assessed lung growth and cardiopulmonary structure and function, and performed transcriptome analyses to identify mechanisms facilitating developmental adaptations to chronic hypoxia. To generate the model, breeding pairs of Sprague-Dawley rats were exposed to hypobaric hypoxia (equivalent to 9,000 feet elevation). Mating, pregnancy and delivery occurred in hypoxic conditions. Six weeks postpartum, structural and functional data were collected in the offspring. RNAseq was performed on right ventricle (RV) and lung tissue. Age-matched breeding pairs and offspring under room air (RA) conditions served as controls. Hypoxic rats exhibited significantly lower body weights and higher hematocrit levels, alveolar volumes, pulmonary diffusion capacities, RV mass, RV systolic pressure as well as increased pulmonary artery remodeling. RNAseq revealed multiple differentially expressed genes in lungs and RVs from hypoxic rats. While there was considerable similarity between hypoxic lungs and RVs compared to RA controls, several upstream regulators unique to lung or RV were identified. We noted a pattern of immune down-regulation and regulation patterns of immune and hormonal mediators similar to the genome from patients with pulmonary arterial hypertension. In summary, we developed a novel murine model of chronic hypoxia exposure that demonstrates functional and structural phenotypes similar to human adaptation. We identified transcriptomic alterations that suggest potential mechanisms for adaptation to chronic HA.
2020-09-30 | GSE140146 | GEO
Project description:Mechanisms driving adaptive developmental responses to chronic high-altitude (HA) exposure are incompletely known. We developed a novel rat model mimicking the human condition of cardiopulmonary adaptation to HA starting at conception and spanning the in utero and postnatal timeframe. We assessed lung growth and cardiopulmonary structure and function and performed transcriptome analyses to identify mechanisms facilitating developmental adaptations to chronic hypoxia. To generate the model, breeding pairs of Sprague-Dawley rats were exposed to hypobaric hypoxia (equivalent to 9,000 ft elevation). Mating, pregnancy, and delivery occurred in hypoxic conditions. Six weeks postpartum, structural and functional data were collected in the offspring. RNA-Seq was performed on right ventricle (RV) and lung tissue. Age-matched breeding pairs and offspring under room air (RA) conditions served as controls. Hypoxic rats exhibited significantly lower body weights and higher hematocrit levels, alveolar volumes, pulmonary diffusion capacities, RV mass, and RV systolic pressure, as well as increased pulmonary artery remodeling. RNA-Seq analyses revealed multiple differentially expressed genes in lungs and RVs from hypoxic rats. Although there was considerable similarity between hypoxic lungs and RVs compared with RA controls, several upstream regulators unique to lung or RV were identified. We noted a pattern of immune downregulation and regulation patterns of immune and hormonal mediators similar to the genome from patients with pulmonary arterial hypertension. In summary, we developed a novel murine model of chronic hypoxia exposure that demonstrates functional and structural phenotypes similar to human adaptation. We identified transcriptomic alterations that suggest potential mechanisms for adaptation to chronic HA.
| S-EPMC7518056 | biostudies-literature
Project description:High-altitude pulmonary hypertension (HAPH) is a severe and progressive disease caused by chronic hypoxia and subsequent pulmonary vascular remodeling. No cure is currently available owing to an incomplete understanding about vascular remodeling. It is believed that hypoxia-induced diseases can be prevented by treating hypoxia. Thus, this study aimed to determine whether daily short-duration reoxygenation at sea level attenuates pulmonary hypertension under high-altitude hypoxia. To this end, a simulated 5,000-m hypoxia rat model was used to evaluate the effect of short-duration reoxygenation. Results show that intermittent, not continuous, short-duration reoxygenation effectively attenuates hypoxia-induced pulmonary hypertension. The mechanisms underlining the protective effects involved that intermittent, short-duration reoxygenation prevented functional and structural remodeling of pulmonary arteries and proliferation, migration, and phenotypic conversion of pulmonary artery smooth muscle cells under hypoxia. The specific genes or potential molecular pathways responsible for mediating the protective effects were also characterised by RNA sequencing.This study is novel in revealing a new potential method in preventing high-altitude pulmonary hypertension. It gives insights into the selection and optimisation of oxygen supply schemes in high-altitude areas.
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Project description:Tibetan chickens exhibit specific adaptations to high-altitude conditions compared with their lowland counterparts. To illustrate the genetic mechanisms of such adaptations in highland chickens, the genomes of four highland and four lowland chicken populations were resequenced. Our results showed that genes under positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune response, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation. The distribution of allele frequencies of non-synonymous single nucleotide polymorphisms between highland and lowland populations was also analyzed by chi-square test. The results showed that several differentially distributed genes with missense mutations were enriched in several functional categories, especially in blood vessel development, which were related to adaptations to hypoxia and intense radiation. RNA sequencing also revealed that several differentially expressed genes were enriched in gene ontology terms related to blood vessel and respiratory system development. Additionally, an evident admixture found in Tibetan chickens suggested a history of introgression from lowland gene pools. Overall, our data provided new insights into the unique adaptation of highland animals to extreme environments.
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Project description:This study evaluates genetic and phenotypic variation in the intermediate altitude Calchaquà population living in the Calchaquà Valleys of the Argentinean Andes in the town of Cachi at 2300 m. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to moderate hypoxia at a intermediate altitude. DNA from 24 saliva samples of CalchaquÃes living at 2300 m in Cachi in the Province of Salta in Argentina was genotyped.
2014-04-05 | E-GEOD-56518 | biostudies-arrayexpress
Project description:This study evaluates genetic and phenotypic variation in the intermediate altitude Calchaquí population living in the Calchaquí Valleys of the Argentinean Andes in the town of Cachi at 2300 m. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to moderate hypoxia at a intermediate altitude.
2014-04-05 | GSE56518 | GEO
Project description:Background: High-altitude hypoxia significantly impacts cardiovascular function, but the effects of adipose/metabolic factors on cardiovascular regulation remain unclear. Thus, a deeper understanding of adipose/metabolic factors’ role in cardiovascular function changes is needed. Methods: We assessed lung ventilation function, cardiovascular function, electrocardiogram, plasma CK-MB, sPecam-1, and 11 plasma adipose/metabolic factors in expeditioners at Antarctic Kunlun Station (4087m). To investigate adipose/metabolic factors’ effects and mechanisms on cardiac function, we constructed a rat model exposed to simulated hypobaric hypoxia (5000 m) with the same oxygen concentration as Kunlun Station. Echocardiography, ELISA, histology, and gene and protein expression studies were employed to examine cardiac function changes, pathological alterations, and leptin’s role in cardiac pathology under acute and chronic hypoxic exposure. Results: The Antarctic ice plateau environment significantly altered lung ventilation function, weakened cardiac pumping and contractile function, increased systematic vascular resistance (SVR), induced adaptive changes in cardiac conduction, significantly increased plasma CK-MB and Pecam-1, and significantly reduced plasma leptin, resistin, insulin, and lipocalin-2 levels. Decreased leptin was significantly correlated to cardiopulmonary function. Rats chronically exposed to simulated hypobaric hypoxia at 5000m exhibited pulmonary arterial hypertension (PAH), right ventricular hypertrophy (RVH), impaired left ventricular systolic and diastolic function, and significant deteriorated left ventricular global longitudinal strain (GLS), lateral and radial strains of the myocardium, with increased plasma CK-MB and sPecam-1 in hypoxic rats. Protein levels of leptin/ob-Rb, JAK2/STAT3, PI3K/AKT/GSK3β, and ERK/JNK were decreased in biventricular myocardial tissues of chronic hypoxia-exposed rats, accompanied by increased myocytes hypertrophy, fibrosis, lipid deposition, cell apoptosis, and mitochondrial dysfunction, and decreased metabolic gene levels. Left ventricular transcriptome analysis revealed that decreased myocardial leptin in hypoxic rats regulated cardiac pathology via down-regulated genes related to circadian rhythm, sodium/potassium ion transport, and cell skeleton. Conclusion: Our findings suggest that leptin is a crucial metabolic factor in regulating cardiac pathological changes and cardiac contractile and diastolic function under high altitudes. These regulatory pathways may involve leptin's classical signaling pathways and genes related to circadian rhythm, sodium/potassium ion transport, and cell skeleton in the heart.
2024-01-20 | GSE245300 | GEO
Project description:Additional to GSE1807 A comparative analysis, by expression profiling of maize, was performed to identify novel components in the mechanisms of maize responses to UV-B. Five high-altitude landraces grown from 2,000 to 3,400 m naturally receive higher UV-B fluence than plants at lower altitudes and similar latitudes. These high-altitude landraces were compared directly with a low-altitude line and with literature reports for other temperate maize lines. A microarray analysis demonstrated that among the UV-B responsive transcripts, several types of gene implicated in chromatin remodeling are differentially expressed before and after UV-B treatment in high-altitude lines. RNAi transgenic plants with lower expression of four such chromatin-associated genes exhibited hypersensitivity to UV-B by measurements of leaf arching, increased leaf chlorosis and necrosis, and altered UV-B regulation of selected genes. These results collectively suggest that genes involved in chromatin remodeling are crucial for UV-B acclimation and that some high-altitude lines exhibit adaptations to this challenge.
2005-05-17 | GSE2163 | GEO
Project description:Purpose: Domestic goats distributed in a wide range of habitats and have evolved genetic adaptations to their local environmental conditions. The goal of this study s to investigate the dramatic gene expression changes of goats that are shaped by high altitude adaptation. Methods: We performed RNA-seq on 27 samples from the three hypoxia-sensitive tissues (heart, lung and skeletal muscle) in three indigenous populations residing in distinct altitudes (600 m, 2,000 m and 3,000 m). Results: We identified numerous differentially expressed genes which exhibited distinct expression patterns, and nonsynonymous SNVs-containing genes which highly differentiated between the high- and low-altitude populations. Conclusions: These identified genes have known or potential roles in hypoxia response, and enriched in functional gene categories potentially responsible for high altitude adaptation, are appealing candidates for further investigation of the adaptive evolution in harsh high-altitude environment.
2017-09-06 | GSE66242 | 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