Project description:To determine hypoxia mediated changes in whole blood, normal C57Bl/10 mice were gradually exposed to a chronic hypoxic environment, equivalent to an altitude of 6500m, for 2 weeks in vivo. Control, age-matched mice were maintained under normoxic, normobaric conditions by exposing them to ambient air in Philadelphia (c. 50 mts above sea level).
Project description:High altitude environments are characterized by the unique and unavoidable stress of chronic hypoxia. While much is known about gene expression responses to acute or in vitro hypoxia, less is known about the gene expression profiles of animals exposed to systemic chronic hypoxia, such as that experienced at high elevations. Here we simulated the hypoxic environment of two high altitude elevations,and a third chamber recieved ambient Reno air. Mice were housed in the hypoxic chambers for 32 days. We used microarrays to characterize the differential gene expression in the livers of mice housed in hypoxic environment of 4500 m versus 3000 and 1400 m. We used this data to draw hypotheses related to novel physiological responses to chronic systemic hypoxia Experiment Overall Design: Mice were housed one of three chambers; the first received ambient Reno air (1400 m) and the other two received air mixed with nitrogen such that one chamber simulated the hypoxic environment of 3000 m and the third chamber simulated hypoxic environment of 4500 m. Twelve mice were housed in each chamber for 32 days. Liver were extracted, and RNA from livers of 4 mice were pooled such that each treatment was represented by 3 pooled samples. Eight of the nine arrays were used for data analysis; one array was excluded as several Affymetrix quality control metrics indicated data quality that was not reliable.
Project description:High altitude environments are characterized by the unique and unavoidable stress of chronic hypoxia. While much is known about gene expression responses to acute or in vitro hypoxia, less is known about the gene expression profiles of animals exposed to systemic chronic hypoxia, such as that experienced at high elevations. Here we simulated the hypoxic environment of two high altitude elevations,and a third chamber recieved ambient Reno air. Mice were housed in the hypoxic chambers for 32 days. We used microarrays to characterize the differential gene expression in the livers of mice housed in hypoxic environment of 4500 m versus 3000 and 1400 m. We used this data to draw hypotheses related to novel physiological responses to chronic systemic hypoxia
Project description:We aim to investigate the changes of lung tissue proteomics between rats with lung injury induced by hypobaric hypoxia at high altitude and rats at low altitude, and between rats dealt with DMF in above two kinds of environment.
2025-06-23 | PXD065310 |
Project description:Characteristics of dynamic changes of intestinal flora in rats under high altitude and low oxygen environment
Project description:High altitude exposes humans to hypobaric and hypoxic conditions, which induce various physiological and molecular changes. Recent evidence, mostly from animal models, points towards interaction between circadian rhythms and the hypoxic response, however their human relevance is largely unknown. To examine the interaction between elevated altitude-low oxygen and daily rhythms, we analyzed the effect of different high altitudes in conjunction with day-time on human whole blood transcriptome. We found that high altitude vastly affects the blood transcriptome and unexpectedly, does not necessarily follow a monotonic response to altitude elevation. We observed daily variance in gene expression, which was largely dependent on altitude. Moreover, using digital cytometry approach we estimated the relative changes in abundance of different cell types and found the several immune cell types were responding in a time- and altitude-dependent manner. Taken together, our data shed new light on the transcriptional response to high altitude and its interaction with daily rhythms.
Project description:In this study, we employed an integrated proteomic and metabolomic approach to systematically analyze the proteome and metabolome profiles of SHRs following prolonged exposure to a high-altitude hypoxic environment. Bioinformatics and enrichment analysis revealed that proteins with significant differential expression were predominantly involved in pathways such as oxidative phosphorylation, thermogenesis, TCA cycle, and carbon metabolism. Further analysis indicated that alterations in key metabolites, including thiamine, S-adenosylhomocysteine, pantothenic acid, fumaric acid, and homoserine, interact with differentially expressed proteins, collectively contributing to the modulation of blood pressure regulation in SHRs under hypoxic conditions. This research provides new molecular insights into understanding the impact of high-altitude hypoxia on the blood pressure regulatory mechanisms in spontaneously hypertensive rats.
Project description:Rationale: Recent studies suggest a potential link between gut bacterial microbiota dysbiosis and PAH, but the exact role of gut microbial communities, including bacteria, archaea, and fungi, in PAH remains unclear. Objectives: To investigate the role of gut microbiota dysbiosis in idiopathic pulmonary arterial hypertension (IPAH) and to assess the therapeutic potential of fecal microbiota transplantation (FMT) in modulating PAH progression. Methods: Using shotgun metagenomics, we analyzed gut microbial communities in IPAH patients and healthy controls. FMT was performed to transfer gut microbiota from IPAH patients or MCT-PAH rats to normal rats and from healthy rats to MCT-PAH rats. Hemodynamic measurements, echocardiography, histological examination, metabolomic and RNA-seq analysis were conducted to evaluate the effects of FMT on PAH phenotypes. Measurements and Main Results: Gut microbiota analysis revealed significant alterations in the bacterial, archaeal, and fungal communities in IPAH patients compared to healthy controls. FMT from IPAH patients induced PAH phenotypes in recipient rats. Conversely, FMT from healthy rats to IPAH rats significantly ameliorated PAH symptoms, restored gut microbiota composition, and normalized serum metabolite profiles. Specific microbial species were identified with high diagnostic potential for IPAH, improving predictive performance beyond individual or combined microbial communities. Conclusions: This study establishes a causal link between gut microbiota dysbiosis and IPAH and demonstrates the therapeutic potential of FMT in reversing PAH phenotypes. The findings highlight the critical role of bacterial, archaeal, and fungal communities in PAH pathogenesis and suggest that modulation of the gut microbiome could be a promising treatment strategy for PAH.