Mus musculus strain:C57BL6J
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA304075 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a proliferative endothelial cell phenotype, inflammation and pulmonary vascular remodeling. BMPR2 loss-of-function has been linked to pathologic plexiform lesions with obliteration of distal pulmonary arteries distal pulmonary arteries BMPR2 silencing inprimary human pulmonary artery ECs (HPAECs) recapitulate important aspects of cellular dysfunction and deregulated signaling associated with PAH. Primary HPAECs were transfected with gene-specific siRNA pools targeting BMPR2 or control siRNA followed PMA or control stimulation.
2015-12-04 | E-GEOD-70456 | biostudies-arrayexpress
Project description:Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that culminates in right heart failure. Vascular pathology in PH is characterized by pulmonary vasoconstriction and progressive vascular remodeling processes that affects all layers of the vascular wall (intima, media and adventitia).
2022-06-09 | GSE194080 | GEO
Project description:Pulmonary hypertension (PH) is a life-threatening disease, characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary arterial pressure and right heart hypertrophy. PH is caused, among other factors, by chronic hypoxia, leading to hyper-proliferation of pulmonary arterial smooth muscle cells (PASMC) and apoptosis-resistant pulmonary microvascular endothelial cells (PMVEC). Upon re-exposure to normoxia, chronic hypoxia-induced PH in mice is reversible. In this study, we aim to identify novel candidate genes involved in pulmonary vascular remodeling specifically in the pulmonary vasculature.
2022-09-01 | GSE183908 | GEO
Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a proliferative endothelial cell phenotype, inflammation and pulmonary vascular remodeling. BMPR2 loss-of-function has been linked to pathologic plexiform lesions with obliteration of distal pulmonary arteries distal pulmonary arteries BMPR2 silencing inprimary human pulmonary artery ECs (HPAECs) recapitulate important aspects of cellular dysfunction and deregulated signaling associated with PAH.
2015-12-04 | GSE70456 | GEO
Project description:Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach.
2023-10-30 | PXD046218 | JPOST Repository
Project description:	Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach.
2024-04-10 | PXD050923 | JPOST Repository
Project description:Rationale: Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease by whole-lung transcriptome analysis. Methods: Wildtype mice were experimentally exposed to S. mansoni ova by intraperitoneal sensitization followed by tail vein augmentation, and the phenotype assessed by right ventricular catheterization and tissue histology, RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, the latter analyzed using 2 bioinformatic methods. Functional testing of the candidate IL-6 pathway was determined using IL6-knockout mice and the STAT3 inhibitor STI-201. Results: Wild-type mice exposed to S. mansoni had increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole lung transcriptome analysis identified the IL6-STAT3-NFATc2 pathway as being upregulated, which was confirmed by PCR and immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL6 or treated with STI-201 developed pulmonary hypertension associated with significant intima remodeling after exposure to S. mansoni. Conclusions: Whole lung transcriptome analysis identified upregulation of the IL6-STAT3-NFATc2 pathway, and IL6 signaling was found to be protective against Schistosoma-induced intimal remodeling. Affy Mouse ST1.0 chip used. Whole lung transcriptome of 3 mice with experimental Schistosoma-induced pulmonary hypertension, compared to 3 control mice. All mice on a C57Bl6/J background.
2013-07-16 | E-GEOD-48936 | biostudies-arrayexpress
Project description:Rationale: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Objectives: To determine whether upregulation of fatty-acid binding protein 4 and 5 (FABP4/5) is critical in pathogenesis of PAH. Methods: FABP4/5 expression was examined in pulmonary arterial endothelial cells (PAECs) and lung tissues from patients with idiopathic PAH and pulmonary hypertension (PH) rat models. Plasma proteome analysis was performed in human PAH samples. Echocardiography, hemodynamics, histology, and immunostaining were performed to evaluate the lung and heart PH phenotypes in Egln1Tie2Cre (CKO) mice and Egln1Tie2Cre/Fabp4-5-/- (TKO) mice. Measurement and Main Results: Both FABP4 and FABP5 were highly induced in ECs of CKO mice and PAECs from IPAH patients, and in whole lungs of PH rats. Plasma levels of FABP4/5 were upregulated in IPAH patients and directly correlated with severity of hemodynamics and biochemical parameters. Genetic deletion of both Fabp4 and 5 in CKO mice caused a reduction of right ventricular systolic pressure (RVSP) and RV hypertrophy, attenuated pulmonary vascular remodeling and prevented the right heart failure. Fabp4/5 deletion also normalized EC glycolysis, reduced ROS and HIF-2a expression, and decreased aberrant EC proliferation in CKO lungs. Conclusions: PH causes aberrant expression of FABP4/5 in pulmonary ECs which leads to enhanced EC glycolysis and hyperproliferation, contributing to the accumulation of arterial ECs and vascular remodeling and exacerbating the disease.
2024-08-02 | GSE261445 | GEO
Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary artery pressure caused by pathological pulmonary artery remodeling. Here, we show that endothelial cell (EC) senescence plays a negative role in pulmonary hypertension via juxtacrine interaction with smooth muscle cells (SMCs). By using EC-specific progeroid mice that we recently generated, we discovered that EC progeria deteriorated vascular remodeling in the lungs, and exacerbated pulmonary hypertension in mice exposed to chronic hypoxia. Mechanistically, senescent ECs overexpressed Notch ligands, which resulted in increased Notch signaling and activated proliferation and migration capacities in neighboring SMCs. Pharmacological inhibition of Notch signaling reduced the effects of senescent ECs on SMCs functions in vitro, and improved the worsened pulmonary hypertension in EC-specific progeroid mice in vivo. Our findings show that EC senescence is a critical disease-modifying factor in PAH and that EC-mediated Notch signaling is a pharmacotherapeutic target for the treatment of PAH, particularly in the elderly.
2023-04-30 | GSE228491 | GEO
Project description:Pulmonary hypertension worsens outcome in left heart disease. Stiffening of the pulmonary artery may drive this pathology by increasing right ventricular dysfunction and lung vascular remodeling. We showed that pulmonary arteries from patients with left heart disease are characterized by increased stiffness that correlates with impaired pulmonary hemodynamics. Pulmonary arteries in left heart disease patients with pulmonary hypertension were characterized by degradation of elastic fibers paralleled by an accumulation of fibrillar collagens. We utilized RNA sequencing to identify differentially expressed genes regulating extracellular matrix remodeling in pulmonary arteries of left heart disease patients with or without pulmonary hypertension, in comparison to healthy-heart donor controls. As such we identified that transcriptional deregulation of extracellular matrix constituents and their regulators precedes clinical pulmonary hypertension, and therefore might be a pathomechanism that drives pulmonary arterial remodeling and stiffening in left heart disease.
2023-07-03 | GSE236251 | GEO