Whole transcriptome analysis of hypoxic pulmonary hypertension
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE159668 | GEO | 2021/09/01
REPOSITORIES: GEO
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Project description:17β-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis in the hypoxic lung, we performed a microarray analysis in lungs from HPH rats treated with E2 (75 mcg/kg/d) ± ER-antagonist ICI182,780 (3 mg/kg/d). Untreated HPH rats and normoxic rats served as controls. Using a false discovery rate of 10%, we identified a significantly differentially regulated genome in E2-treated vs. untreated hypoxia rats. Genes most up-regulated by E2 encoded matrix metalloproteinase 8, S100 calcium binding protein A8, and IgA Fc receptor; genes most down-regulated by E2 encoded olfactory receptor 63, secreted frizzled-related protein 2, and thrombospondin 2. Several genes affected by E2 changed in the opposite direction after ICI182,780 co-treatment, indicating an ER-regulated genome in HPH lungs. The bone morphogenetic protein antagonist Grem1 (gremlin 1) was up-regulated by hypoxia, but found to be among the most down-regulated genes after E2 treatment. Gremlin 1 protein was reduced in E2-treated vs. untreated hypoxic animals, and ER-blockade abolished the inhibitory effect of E2 on Grem1 mRNA and protein. In conclusion, E2 ER-dependently regulates several genes involved in proliferative and inflammatory processes during hypoxia. Gremlin 1 is a novel target of the E2-ER axis in HPH. Understanding the mechanisms of E2 gene regulation in HPH may allow for selectively harnessing beneficial transcriptional activities of E2 for therapeutic purposes.
2017-08-01 | GSE85618 | GEO
Project description:lncRNA-sequencing in a rat model of hypoxic pulmonary hypertension (HPH)
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Project description:These microarray studies were performed using whole lungs of BALB/C mice during development of hypoxia-induced pulmonary hypertension (days 1-21) and resolution of pulmonary hypertension after return to normoxia (days 22-35) . Mice were sampled during nine time-points and each time-point was replicated 4 times (with dye swapping). Keywords = hypoxia Keywords = pulmonary hypertension
2010-06-10 | E-GEOD-1909 | biostudies-arrayexpress
Project description:Whole transcriptome analysis of hypoxic pulmonary hypertension
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Project description:The potential roles of mRNAs and lncRNAs in the development and the reoxygenation treatment of reversal of hypoxic pulmonary hypertension are still unknown. 24 healthy adult male C57/BL6 mice were divided into three groups (normoxia group, hypoxia group, hypoxia-normoxia group), lncRNA and mRNA microarray was performed，meanwhile，the changes of right ven-tricular systolic pressure (RVSP) and other physiological indexes were measured in the three groups. The results showed that the index of RVSP, the right ventricular hypertrophy index RV/(LV+S), pulmonary artery walls and the muscularization ratio of pulmonary arterioles were significantly increased after Hypoxia treatment, while they were attenuated after the normoxia condition restored. Moreover, the study revealed there were 62 lncRNAs and 99 mRNAs with significant difference expression were associated with the reversal of hypoxic pulmonary hypertension by reoxygenation in mice. Furthermore, the pathway enrichment and gene ontology analysis of 99 DEGS were performed. Interestingly, the result suggested that chemokine subfamily CCL2/ CXCL played a role in the occurrence, development and reversion of pulmonary hypertension by reoxygenation. This study was the first time to demonstrate the transcriptome profiles of lncRNAs and mRNAs in the lung tissue during the reversal of hypoxic pulmonary hypertension in mice by reoxygenation, which might further broaden the understanding of the pathogenesis and the therapeutic effect of oxygen recovery of hypoxic pulmonary hypertension.
2021-03-04 | GSE168159 | GEO
Project description:These microarray studies were performed using whole lungs of BALB/C mice during development of hypoxia-induced pulmonary hypertension (days 1-21) and resolution of pulmonary hypertension after return to normoxia (days 22-35) . Mice were sampled during nine time-points and each time-point was replicated 4 times (with dye swapping). Keywords = hypoxia Keywords = pulmonary hypertension Keywords: other
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Project description:m7G-MeRIP-sequencing in a rat model of hypoxic pulmonary hypertension (HPH)
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Project description:Hypoxia can induce vasoconstriction followed by vascular remodeling including hypertrophy and hyperplasia of pulmonary vascular smooth muscle and proliferation of endothelial cells. The goal of this project is to elucidate the genes involved in vascular remodeling following pulmonary hypertension. Total RNA was isolated from lungs of normoxic and hypoxic treated animals.
2007-12-13 | E-GEOD-482 | biostudies-arrayexpress
Project description:Studies in various animal models suggest an important role for pulmonary macrophages in the pathogenesis of pulmonary hypertension (PH). Yet, the molecular mechanisms characterizing the functional macrophage phenotype relative to time and pulmonary localization/compartmentalization remain largely unknown. Here, we utilized a hypoxic murine model of PH in combination with flow cytometry assisted cell sorting (FACS) to quantify and isolate lung macrophages from two compartments over time and characterized their programing via RNA sequencing (RNAseq) approaches. In response to hypoxia, we found an early increase in macrophage number that was restricted to the interstitial/perivascular compartment, without recruitment of macrophages to the alveolar compartment or changes in the number of resident alveolar macrophages. Principle component analysis demonstrated significant differences in overall gene expression between alveolar (AMs) and interstitial macrophages (IMs) at baseline and after 4 and 14 days hypoxic exposure. AM’s at both day 4 and 14 and IM’s at day 4 shared a conserved “hypoxia program” characterized by mitochondrial dysfunction, pro-inflammatory gene activation and mTORC1 signaling, while IM’s at day 14 demonstrated a unique anti-inflammatory/ pro-reparative programming state. We conclude that the pathogenesis of vascular remodeling in hypoxic PH involves an early compartment independent activation of lung macrophages towards a conserved hypoxia program, with the development of compartment specific programs later on in the course of disease. Thus, harnessing time and compartment specific differences in lung macrophage polarization needs to be considered in the therapeutic targeting of macrophages in hypoxic PH and potentially other inflammatory lung diseases.
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Project description:Arterial pulmonary hypertension is a rare disease, with little knowledge regarding its etiology, and high mortality. Development of right and later on also left ventricular heart insufficiency, secondary to pulmonary hypertension, is a negative predictive factor. Genetic and molecular processes underlying left heart ventricle remodeling over the course of pulmonary hypertension remain unknown. In particular, there is no knowledge regarding the mechanisms of left heart ventricle atrophy which was completely avoided by researchers until recently.The aim of this study was to assess changes in protein abundance in left and right heart ventricle free wall of rats in monocrotaline model of PAH.
2020-09-07 | PXD015896 | Pride