Effect of donepezil on lung fibrosis related pulmonary hypertension
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE211224 | GEO | 2023/02/16
REPOSITORIES: GEO
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Project description:Whole lung RNA-seq of 8 mice with experimental Schistosoma-induced pulmonary hypertension, compared to 8 control mice. All mice on a C57Bl6/J background. 3 schisto-PH and 3 control mice (#s 1-3 in each group) were also processed by Affy microarray and separately submitted. 3 of the mice in each group (labeled 1D11) were also treated with the pan-TGF-beta neutralizing antibody 1D11. Illumina HiSeq 2000 used. Data published in: Protective Role of IL6 in Vascular Remodeling in Schistosoma-Pulmonary Hypertension. Graham BB, Chabon J, Kumar R, Kolosionek E, Gebreab L, Debella E, Edwards M, Diener K, Shade T, Bifeng G, Bandeira A, Butrous G, Jones K, Geraci M, Tuder RM. Am J Respir Cell Mol Biol. 2013 Jul 1. [Epub ahead of print] PMID: 23815102 Whole lung transcriptome of 8 mice with experimental Schistosoma-induced pulmonary hypertension, compared to 8 control mice. All mice on a C57Bl6/J background.
2013-07-23 | E-GEOD-49114 | biostudies-arrayexpress
Project description:Pulmonary hypertension (PH) is a chronic and progressive disease with significant morbidity and mortality. It is characterized by remodeled pulmonary vessels associated with perivascular and intravascular accumulation of inflammatory cells. While there is compelling evidence that bone marrow-derived cells, such as macrophages and T cells, cluster in the vicinity of pulmonary vascular lesions in humans and that they contribute to PH development in different animal models, the role of dendritic cells in PH is less clear. Dendritic cells' involvement in PH is likely since they are responsible for coordinating innate and adaptive immune responses. We hypothesized that dendritic cells drive hypoxic PH. We demonstrate that a classical dendritic cell (cDC) subset (cDC2) is increased and activated in wild-type mouse lungs after hypoxia exposure. We observe significant protection after the depletion of cDCs in ZBTB46 DTR chimera mice before hypoxia exposure and after established hypoxic PH. In addition, we find that cDC depletion is associated with a reduced number of two macrophage subsets in the lung (FolR2+ MHCII+ CCR2+ and FolR2+ MHCII+ CCR2-). We found that depleting cDC2s, but not cDC1s, was protective against hypoxic PH. Finally, proof-of-concept studies in human lungs show increased perivascular cDC2s in patients with Idiopathic Pulmonary Arterial Hypertension (IPAH). Our data points to an essential role of cDCs in the pathophysiology of PH.
2024-08-24 | GSE256348 | GEO
Project description:Right heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets.
2022-10-14 | GSE215341 | GEO
Project description:Pulmonary hypertension (PH) is a common complication of systemic sclerosis (SSc) and a leading cause of mortality among patients with this disease. PH can also occur as an idiopathic condition (idiopathic pulmonary arterial hypertension, iPAH). We sought to investigate the transcriptomic alterations in PH vascular populations to understand cellular mechanisms underlying pathobiology of systemic sclerosis associated and idiopathic pulmonary hypertension.
2024-06-07 | GSE244781 | GEO
Project description:SRY-Box Transcription Factor 17 (SOX17) enhancers variants and mutations are found in patients with pulmonary arterial hypertension (PAH). In human PAH pulmonary microvascular endothelial cells (HPMVEC), there is a significant downregulation of SOX17 expression. We hypothesized that SOX17 deficiency contributes to the pathogenesis of PAH and found that mice with endothelial specific disruption (ecKO Sox17) developed spontaneous pulmonary hypertension (PH) and exacerbated hypoxia-induced PH. Loss of SOX17 in lung ECs induces cell cycle programming, proliferative and anti-apoptotic phenotypes, a process mediated by the activation of E2F Transcription Factor 1 (E2F1) signaling. Pharmacological inhibition of E2F1 in ecKO Sox17 mice attenuated PH and cell cycle programming. Our study demonstrated that endothelial SOX17 deficiency induces PH and targeting E2F1 signaling represents a promising approach in PAH patients.
2023-03-15 | GSE192649 | GEO
Project description:Right ventricular (RV) failure is the major determinant of outcome in pulmonary hypertension (PH). Calves exposed to 2-wks environmental hypoxia develop severe PH and unlike rodents, chronic hypoxia-induced PH in this species can lead to right heart failure. We therefore sought to examine the molecular and structural changes in the RV in calves with hypoxia-induced PH, hypothesizing that we could identify mechanisms underlying compensated physiological function in the face of developing severe PH. Calves were exposed to 14d of hypobaric hypoxia (PB=430 mm Hg, equivalent to 4570m elevation, n=29) or ambient normoxia (1525m, n=25). Cardiopulmonary function was evaluated by right heart catheterization and pressure volume loops. Molecular and cellular determinants of RV remodeling were analyzed by cDNA microarrays, RealTime PCR, proteomics and immunochemistry. Hypoxic exposure induced robust PH, with increased RV contractile performance and preserved cardiac output, yet evidence of dysregulated RV-pulmonary artery mechanical coupling consistent with advanced PH. Analysis of gene expression revealed cellular processes associated with structural remodeling, cell signaling, and survival. We further identified specific clusters of gene expression associated with (i) hypertrophic gene expression and pro-survival mechanotransduction through YAP-TAZ signaling, (ii) ECM remodeling, (iii) inflammatory cell activation and (iv) angiogenesis. A potential transcriptomic signature of cardiac fibroblasts in RV remodeling was detected. Proteomic and immunohistochemical analysis confirmed RV myocyte hypertrophy, together with localization of ECM remodeling, inflammatory cell activation, and endothelial cell proliferation within the RV interstitium. In conclusion, hypoxia and hemodynamic load initiate coordinated processes of protective and compensatory RV remodeling to withstand the progression of PH.
2023-03-20 | GSE217438 | GEO
Project description:We determined pattern of miRNAs of mild-to-severe human pulmonary arterial hypertension and compared the with health controls using microarray and subsequently validated by QPCRs Manuscript Title: Circulating miRNAs as novel marker for pulmonary hypertension. (Under Revision Plos One Manuscript ID: PONE-D-12-38535) Performed microRNA microarray from one healthy and one severe PH patient and compared the results using additional samples by qPCR for other miRNAs
2013-11-01 | E-GEOD-44145 | biostudies-arrayexpress
Project description:Dysfunction of pulmonary arterial endothelial cells (PAECs) is associated with the development and progression of vascular pathology. However, it remains unknown how pulmonary hypertension (PH) affects cellular composition and transcriptomic profile of pulmonary endothelium. Here, we have undertaken a single-cell, compartment specific approach to characterise alterations in PAECs associated with two different types of PH, i.e., pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with pulmonary fibrosis (PHPF). Our unbiased analysis showed that endothelium of medium / small caliber pulmonary arteries is composed of three subsets of endothelial cells (ECs). The analysis of healthy and PH endothelium revealed that the three populations are persistently represented in remodelled arteries. Additionally, an exploratory analysis of human aorta (AO) and coronary arteries (CA) endothelium revealed that, although similar gene expression patterns were noticeable, PAECs subpopulations proportions differs significantly from pulmonary arteries (PA) endothelium. To address whether EC heterogeneity is a prime feature of human endothelium, we also performed a similar analysis in a murine model of hypoxia, revealing that similar EC populations were evident in this animal model. Comparative analysis of EC subpopulations in healthy and PH EC identified a common genetic deregulation accompanying vascular remodelling. Even though murine EC displayed some similarities with human EC subpopulations, the intense re-programming associated with hypoxia associated vascular remodelling displayed significant differences compared to the human disease. Finally, in depth comparative analysis of PAH and PHPF EC highlighted the development of disease-specific transcriptomic alterations in the three populations. Therefore, characterisation of transcriptomic differences in the endothelial bed of PAH and PHPF patients can facilitate identification of novel, disease-specific therapeutic targets.
2024-07-11 | GSE228643 | 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: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.
2012-04-30 | GSE33463 | GEO