PAH sequencing study
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001005532 | EGA |
REPOSITORIES: EGA
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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.
2016-07-15 | E-GEOD-84395 | biostudies-arrayexpress
Project description:Pulmonary arterial hypertension (PAH) affects approximately 10% of patients with systemic sclerosis (SSc) and is a leading cause of death. We sought to identify serum cytokine signatures that risk stratify SSc patients for this potentially fatal complication. In the current study we aimed to characterize specific cytokine signatures that differentiate patients with incident SSc-PAH, patients at high risk for SSc-PAH, patients at low risk for SSc-PAH, and healthy controls. We anticipate these data will assist with early identification of patients at high risk for or with incident SSc-PAH. Additionally, we expect this study will identify cytokines that may be involved in the pathogenesis of SSc-PAH and could serve as therapeutic targets.
2025-01-20 | GSE195583 | GEO
Project description:Pulmonary arterial hypertension (PAH) affects approximately 10% of patients with systemic sclerosis (SSc) and is a leading cause of death. We sought to identify serum cytokine signatures that risk stratify SSc patients for this potentially fatal complication. In the current study we aimed to characterize specific cytokine signatures that differentiate patients with incident SSc-PAH, patients at high risk for SSc-PAH, patients at low risk for SSc-PAH, and healthy controls. We anticipate these data will assist with early identification of patients at high risk for or with incident SSc-PAH. Additionally, we expect this study will identify cytokines that may be involved in the pathogenesis of SSc-PAH and could serve as therapeutic targets.
2025-01-20 | GSE195581 | GEO
Project description:Comparison of miRNA expression between patients with idiopathic and systemic sclerosis PAH and healthy controls and systemic sclerosis without PAH
2021-06-01 | E-MTAB-10425 | biostudies-arrayexpress
Project description:Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by pulmonary arteriolar remodeling, and is frequently associated with right heart failure. This study identifies significant novel biological changes in eight genes and several genetic pathways, that were likely to contribute to the pathogenesis of PAH. We also demonstrate that PAH and PH secondary to idiopathic pulmonary fibrosis (IPF) are characterized by distinct gene expression signatures, implying distinct pathophysiological mechanisms. Keywords: disease versus control Keywords: Expression profiling by array
2010-01-22 | GSE15197 | GEO
Project description:<p>Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, most studies have focused on the bacterial community and the exact role and mechanisms of multi-kingdom gut microbiota, including bacteria, archaea and fungi in PAH remains largely unclear. Idiopathic PAH (IPAH) patients exhibited distinct gut microbiota profiles with altered bacterial, archaeal and fungal compositions compared to healthy controls. Fecal microbiota transplantation (FMT) from IPAH patients or monocrotaline (MCT)-induced PAH rats to antibiotic treated rats induced PAH phenotypes, including increased right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling. Conversely, FMT from normal rats to MCT-PAH rats ameliorated PAH symptoms and reversed multi-kingdom gut microbiota dysbiosis. Metabolomics revealed significant alterations in plasma metabolites. Our findings established a causal link between multi-kingdom gut microbiota dysbiosis and PAH, demonstrating the therapeutic potential of FMT in reversing PAH phenotypes. More importantly, in addition to gut bacteria, gut archaeal and fungal communities also significantly correlate with PAH pathogenesis, highlighting their indispensable role in the gut.</p>
2025-05-12 | MTBLS10563 | MetaboLights
Project description:Heritable epigenetic adaptation to environmental stressors is a compelling but highly contested possibility. Previously, we showed evidence of a generationally heritable epigenetic memory at the cytochrome P450 1A (CYP1A) gene in wild Atlantic killifish (Fundulus heteroclitus) with evolved tolerance to PAH. This memory leads to blunted induction of CYP1A by PAH; this blunting that protects against polycyclic aromatic hydrocarbon (PAH)-induced cancer. Here, using Oxford Nanopore long-read sequencing in PAH-tolerant and sensitive wild-type embryos, we show that genome-wide, PAH-tolerant embryos showed reduced plasticity in DNA methylation response to PAH vs. PAH sensitive embryos that was not due to mutational loss of CpG sites. Notably, we observed population differences in gene methylation in pathways linked to the PAH tolerance phenotype, including AHR and voltage-gated potassium channel signaling, as well as developmental processes and energy metabolism. Specifically, we observed PAH-induced loss of CYP1A gene body methylation in PAH-sensitive (86% CpG methylation in control, decreased to 63% in exposed), but not -tolerant (84% control, 86% exposed), embryos. We observed similar patterns at CYP1B, CYP1C, and the aryl hydrocarbon receptor repressor, AHRR, which show similarly blunted expression. This genic methylation loss was correlated with decreased levels of natural anti-sense RNA transcripts in cis (cis-NATs), which may regulate transcription of these genes. Our data support the existence of stable epigenetic responses to chronic environmental stressors in a natural experimental setting, with broad implications for natural or directed adaptation strategies for other populations.
2026-01-07 | GSE313974 | GEO
Project description:Heritable epigenetic adaptation to environmental stressors is a compelling but highly contested possibility. Previously, we showed evidence of a generationally heritable epigenetic memory at the cytochrome P450 1A (CYP1A) gene in wild Atlantic killifish (Fundulus heteroclitus) with evolved tolerance to PAH. This memory leads to blunted induction of CYP1A by PAH; this blunting that protects against polycyclic aromatic hydrocarbon (PAH)-induced cancer. Here, using Oxford Nanopore long-read sequencing in PAH-tolerant and sensitive wild-type embryos, we show that genome-wide, PAH-tolerant embryos showed reduced plasticity in DNA methylation response to PAH vs. PAH sensitive embryos that was not due to mutational loss of CpG sites. Notably, we observed population differences in gene methylation in pathways linked to the PAH tolerance phenotype, including AHR and voltage-gated potassium channel signaling, as well as developmental processes and energy metabolism. Specifically, we observed PAH-induced loss of CYP1A gene body methylation in PAH-sensitive (86% CpG methylation in control, decreased to 63% in exposed), but not -tolerant (84% control, 86% exposed), embryos. We observed similar patterns at CYP1B, CYP1C, and the aryl hydrocarbon receptor repressor, AHRR, which show similarly blunted expression. This genic methylation loss was correlated with decreased levels of natural anti-sense RNA transcripts in cis (cis-NATs), which may regulate transcription of these genes. Our data support the existence of stable epigenetic responses to chronic environmental stressors in a natural experimental setting, with broad implications for natural or directed adaptation strategies for other populations.
2026-01-07 | GSE313975 | GEO
Project description:The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells. The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated PAH patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and PH (SSC-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Gene expression is compared at a global level using total RNA from BPMC for pateints and controls using the Illumina microarray platform.
2012-04-29 | E-GEOD-33463 | biostudies-arrayexpress
Project description:<p>The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO.</p> <p>The syndrome of pulmonary hypertension (PH) is a pulmonary disease that carries very high morbidity and mortality. Pulmonary arterial hypertension (PAH) is a category of PH (WHO Group 1) that includes several entities (idiopathic or heritable PAH, and PAH associated with other diseases such as connective tissue diseases including scleroderma-associated PAH) and carries a dismal prognosis, in particular when it relates to scleroderma-associated PAH (median survival of about 4 years). It is believed that the severity of structural changes involving the pulmonary vasculature and right ventricular failure are genetically determined. The 'Genomics and Genetics of Pulmonary Arterial Hypertension' study at Johns Hopkins University aims to identify genetic determinants associated with risk of PAH in a cohort of European American and African American participants with and without PAH. The study also focuses on patients with scleroderma, who are further stratified according to those who have or do not have PAH. The broad goals of the Lung GO/ESP-GO falls into two general categories: (i) discovery of all variants (i.e., common and rare) in all protein-coding regions of the human genome (i.e., the exome) conferring risk to complex pulmonary diseases including PAH. The Johns Hopkins University PAH cohort offers a unique opportunity to elucidate genetic variants that cause PAH.</p>
| phs000290 | dbGaP