Role of Flk1 in pulmonary arterial hypertension [Flox]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216682 | GEO | 2023/08/25
REPOSITORIES: GEO
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Project description:Microarray analysis of peripheral blood mononuclear (PBMC) cells in pulmonary arterial hypertension. Keywords = mononuclear cells Keywords = gene microarray Keywords = pulmonary arterial hypertension Keywords = Herpesvirus Keywords = biomarker Keywords: other
2003-11-15 | GSE703 | GEO
Project description:Despite recent improvements in management of idiopathic pulmonary arterial hypertension, mortality remains high. Understanding the alterations in the transcriptome–phenotype of the key lung cells involved could provide insight into the drivers of pathogenesis. In this study, we examined differential gene expression of cell types implicated in idiopathic pulmonary arterial hypertension from lung explants of patients with idiopathic pulmonary arterial hypertension compared to control lungs. After tissue digestion, we analyzed all cells from three idiopathic pulmonary arterial hypertension and six control lungs using droplet-based single cell RNA-sequencing. After dimensional reduction by t-stochastic neighbor embedding, we compared the transcriptomes of endothelial cells, pericyte/smooth muscle cells, fibroblasts, and macrophage clusters, examining differential gene expression and pathways implicated by analysis of Gene Ontology Enrichment. We found that endothelial cells and pericyte/smooth muscle cells had the most differentially expressed gene profile compared to other cell types. Top differentially upregulated genes in endothelial cells included novel genes: ROBO4, APCDD1, NDST1, MMRN2, NOTCH4, and DOCK6, as well as previously reported genes: ENG, ORAI2, TFDP1, KDR, AMOTL2, PDGFB, FGFR1, EDN1, and NOTCH1. Several transcription factors were also found to be upregulated in idiopathic pulmonary arterial hypertension endothelial cells including SOX18, STRA13, LYL1, and ELK, which have known roles in regulating endothelial cell phenotype. In particular, SOX18 was implicated through bioinformatics analyses in regulating the idiopathic pulmonary arterial hypertension endothelial cell transcriptome. Furthermore, idiopathic pulmonary arterial hypertension endothelial cells upregulated expression of FAM60A and HDAC7, potentially affecting epigenetic changes in idiopathic pulmonary arterial hypertension endothelial cells. Pericyte/smooth muscle cells expressed genes implicated in regulation of cellular apoptosis and extracellular matrix organization, and several ligands for genes showing increased expression in endothelial cells. In conclusion, our study represents the first detailed look at the transcriptomic landscape across idiopathic pulmonary arterial hypertension lung cells and provides robust insight into alterations that occur in vivo in idiopathic pulmonary arterial hypertension lungs.
2021-03-24 | GSE169471 | GEO
Project description:To investigate the role of Flk1 in pulmonary arterial hypertension, we observed the behavior of Flk1 in a disease model using Flk1-GFP mice. Gene expression profiling analysis was performed using data obtained from RNA-seq of Flk1-positive cells on days 1 and 8 of hypoxia exposure, when Flk1 changes were greatest.
2023-08-25 | GSE216681 | GEO
Project description:Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation.
2016-07-15 | GSE84395 | GEO
Project description:Pulmonary arterial hypertension (PAH) is a severe and incurable pulmonary vascular disease. One of the primary origins of PAH is pulmonary endothelial dysfunction leading to vasoconstriction, aberrant angiogenesis and smooth muscle cell proliferation, endothelial-to-mesenchymal transition, thrombosis and inflammation. Our objective was to study the epigenetic variations in pulmonary endothelial cells (PEC) through a specific pattern of DNA methylation. DNA was extracted from cultured PEC from patients with idiopathic PAH (n=11), heritable PAH (n=10) and controls (n=18). ). DNA methylation was assessed using the Illumina HumanMethylation450 Assay. After normalization, samples and probes were clustered according to their methylation profile. Differential clusters were functionally analysed using bioinformatics tools.
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Project description:Pulmonary arterial hypertension (PAH) is a progressive disease in which pulmonary arterial (PA) endothelial cell (EC) dysfunction is associated with unrepaired DNA damage. BMPR2 is the most common mutant gene in PAH. We report that human PAEC with reduced BMPR2 have persistent DNA damage in room air after hypoxic exposure (reoxygenation), as do mice with EC deletion of Bmpr2 (EC-Bmpr2-/-) and persistent pulmonary hypertension. Similar findings are observed in PAEC with loss of the DNA damage sensor ATM, and in mice with Atm deleted in EC (EC-Atm-/-). Gene expression analysis of EC-Atm-/- and EC-Bmpr2-/- lung EC revealed reduced Foxf1, a transcription factor with relative selectivity for lung EC. Reducing FOXF1 in control PAEC induced DNA damage and impaired angiogenesis whereas transfection of FOXF1 in PAH PAEC repaired DNA damage and restored angiogenesis. Lung EC targeted delivery of Foxf1 to reoxygenated EC-Bmpr2-/- mice repaired DNA damage, induced angiogenesis and reversed pulmonary hypertension.
2023-08-15 | GSE215933 | GEO
Project description:miRNAs have been proved to participate in the regulation of proliferation and apoptosis in many diseases,we consider there may be associations between miRNAs and development of pulmonary arterial hypertension (PAH). Previous studies have revealed that several miRNAs participated in the regulation of the development of PAH. In this study, we investigated the miRNA differential expression spectrum in pulmonary arterial hypertension patients.
2021-10-01 | E-MTAB-10932 | biostudies-arrayexpress
Project description:CAV1 loss-of-function mutations have been associated with the development of pulmonary arterial hypertension (PAH). CAV1 is an integral component of endothelial caveolae, specialized lipid rafts that attach to the actin cytoskeleton and modulate receptor/signal transduction coupling. CAV1 loss in pulmonary artery endothelial cells produced a proliferative, hypermigratory cellular phenotype with a disrupted cytoskeletal architecture, mirroring known features of PAH pathobiology. Gene expression on Human Pulmonary Arterial Endothelial Cells (PAECs) transfected with non-targeting siRNA control pool or siRNA (ON-TARGET plus CAV1) in the presence or absence of TNF-alpha was evaluated
2021-02-24 | GSE138991 | GEO
Project description:Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. Global profiles were determined in human lung tissue and compared across 11 normal and 12 severe pulmonary arterial hypertension patients. Using a combination of microarray and high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung.
2014-11-14 | E-GEOD-53408 | biostudies-arrayexpress
Project description:The goal of this study is to compare transcriptome profiling (RNA-seq) in controls, unaffected BMPR2 mutation carriers and affected familial pulmonary arterial hypertension patients, to elucidate a protective feature in iPS derived endothelial cells from the mutation carriers.
2017-01-18 | GSE79613 | GEO