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Transcriptional changes of the extracellular matrix in chronic thromboembolic pulmonary hypertension governs right ventricle remodeling and recovery [ext327_rnaseq]

ABSTRACT: The present prospective study included a total number of 3 patients with a final diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), who were treated by pulmonary endarterectomy (PEA) at the Kerckhoff Heart and Thorax Center between 2016 and 2020. Biopsies of the myocardial interventricular septum from 3 patients were collected at baseline (BL) before PEA surgery (pre-septal-PEA) In this case, to account for technical and safety aspects, the specimens were taken from the myocardial interventricular septum. The aim of the Study was a comparative characterization of RNA-profiles of septum in CTEPH patients after PEA surgery (postPEA) compared to before PEA surgery (pre-septal-PEA).

ORGANISM(S): Homo sapiens

PROVIDER: GSE249694 | GEO | 2024/04/18

REPOSITORIES: GEO

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Transcriptional changes of the extracellular matrix in chronic thromboembolic pulmonary hypertension governs right ventricle remodeling and recovery [ext395_rnaseq]

Project description:The present prospective study included a total number of 71 patients with a final diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), who were treated by pulmonary endarterectomy (PEA) at the Kerckhoff Heart and Thorax Center between 2016 and 2020. Biopsies of the free right ventricular wall from 71 patients were collected at baseline (BL) during PEA. In a subgroup of 24 patients, myocardial interventricular septum biopsie were obtained during right heart catheterization (RHC) 12 months after PEA (postPEA) In this case, to account for technical and safety aspects, the specimens were taken from the myocardial interventricular septum. Patients were grouped in severe, intermediat and moderate risk according to 1 year mortality risk by applying a modified version of the European Society of Cardiology (ESC) guidelines risk stratification model according to their BL characteristics. The aim of the Study was: a) A comparative characterization of RNA-profiles in CTEPH patients with disease status at baseline prior to PEA therapy; b): An assessment of dynamics of the RNA-profiles in CTEPH patients pre and post PEA.

2024-04-18 | GSE249696 | GEO

Transcriptional changes of the extracellular matrix in chronic thromboembolic pulmonary hypertension governs right ventricle remodeling and recovery [ext128_rnaseq]

Project description:The present prospective study included a total number of 9 patients with a final diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), who were treated by pulmonary endarterectomy (PEA) at the Kerckhoff Heart and Thorax Center between 2016 and 2020. Biopsies of theright ventricularfreewall from9patients were collected at baseline (BL) before PEA surgery (prePEA). Patients were grouped in severe and moderate risk groups according to 1 year mortality risk by applying a modified version of the European Society of Cardiology (ESC) guidelines risk stratification model according to their BL characteristics. The aim of the Study was a comparative characterization of RNA-profiles in CTEPH patients with disease status at baseline prior to PEA therapy

2024-04-18 | GSE249691 | GEO

Transcriptome profile of fibroblasts in chronic thromboembolic pulmonary hypertension

Project description:The hallmark of chronic thromboembolic pulmonary hypertension (CTEPH) is fibrotic transformation of pulmonary arterial thrombus, leading to mechanical obstruction of pulmonary arteries. We report the transcriptome profile of fibroblasts isolated from pairs of CTEPH thrombus and pulmonary artery adventitia of the same patient. Fibroblasts isolated from CTEPH thrombus demonstrated upregulation of genes associated with the TGF-β pathway indicating that TGF-β upregulation is associated with the intravascular remodeling process.

2020-12-31 | GSE149413 | GEO

The significance of CD16+ monocytes in the occurrence and development of Chronic Thromboembolic Pulmonary Hypertension: insights from single-cell RNA sequencing

Project description:Our current understanding of the pathobiology of chronic thromboembolic pulmonary hypertension (CTEPH) is primarily based on studies using specimens obtained through pulmonary endarterectomy (PEA). However, there is a significant gap in our knowledge regarding the characteristics and functions of circulating immune cells in CTEPH patients. To address this gap, our study aims to characterize the peripheral blood circulating immune cells in CTEPH patients, with a particular focus on monocytes. In this study, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) extracted from five CTEPH patients. This approach allowed us to identify various immune cell types present in the peripheral blood, including monocytes, T cells, and B cells. Notably, we observed an increased proportion of CD16+ monocytes in CTEPH patients. This monocyte subset exhibited distinct transcriptional profiles, indicating their involvement in critical biological processes such as cell adhesion, T cell activation, coagulation, and platelet activation. Our findings suggest that CD16+ monocytes may play a significant role in the pathogenesis of CTEPH, particularly in pulmonary arterial thrombosis and intimal remodeling. Furthermore, we observed that this subset of monocytes might be recruited into the pulmonary artery intima and differentiate into macrophages characterized by high IL-1β expression, potentially contributing to disease progression. This study provides new insights into the immune landscape of CTEPH and highlights the potential role of CD16+ monocytes in the disease's pathophysiology.

2024-08-10 | GSE274381 | GEO

Anti-proliferative effect of selexipag active metabolite MRE-269 on pulmonary arterial smooth muscle cells from patients with chronic thromboembolic pulmonary hypertension

Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is a group 4 pulmonary hypertension (PH) characterized by non-resolving thromboembolism in the central pulmonary artery and vascular occlusion in the proximal and distal pulmonary artery. Medical therapy is chosen for patients who are ineligible for pulmonary endarterectomy or balloon pulmonary angioplasty or who have symptomatic residual PH after surgery or intervention. Selexipag, an oral prostacyclin receptor agonist and potent vasodilator, was approved for CTEPH in Japan in 2021. To evaluate the pharmacological effect of selexipag on vascular occlusion in CTEPH, we examined how its active metabolite MRE-269 affects platelet-derived growth factor-stimulated pulmonary arterial smooth muscle cells (PASMCs) from CTEPH patients. MRE-269 showed a more potent anti-proliferative effect on PASMCs from CTEPH patients than on those from normal subjects. DNA-binding protein inhibitor genes ID1 and ID3 were found by RNA sequencing and real-time quantitative polymerase chain reaction to be expressed at lower levels in PASMCs from CTEPH patients than in those from normal subjects and were upregulated by MRE-269 treatment. ID1 and ID3 upregulation by MRE-269 was blocked by co-incubation with a prostacyclin receptor antagonist, and ID1 knockdown by small interfering RNA transfection attenuated the anti-proliferative effect of MRE-269. ID signaling may be involved in the anti-proliferative effect of MRE-269 on PASMCs. This is the first study to demonstrate the pharmacological effects on PASMCs from CTEPH patients of a drug approved for the treatment of CTEPH. Both the vasodilatory and the anti-proliferative effect of MRE-269 may contribute to the efficacy of selexipag in CTEPH.

2022-12-27 | GSE221511 | GEO

Expression patterns in chronic thromboembolic pulmonary hypertension

Project description:We sequenced RNA from pulmonary arteries from CTEPH, IPAH or healthy, failed donors

2019-02-18 | GSE84538 | GEO

DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic thromboembolic pulmonary hypertension

Project description:DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic thromboembolic pulmonary hypertension

2018-04-13 | GSE113061 | GEO

Single cell RNA sequencing of distal thrombus tissue from CTEPH patients

Project description:Our current understanding of CTEPH pathobiology is primarily derived from cell-based studies limited by the use of specific cell markers or phenotypic modulation in cell culture. Therefore, our main objective is to identify the multiple cell types that comprise the CTEPH thrombus and to study their dysfunction. Here we used single cell RNA sequencing (scRNAseq) of tissue removed at the time of pulmonary endarterectomy (PEA) surgery from five patients to identify the multiple cell types. Our scRNAseq identify the multiple cell types including macrophages, T cells, and smooth muscle cells, that comprise CTEPH thrombus. Notably, multiple macrophage subclusters were identified but broadly split into two categories, with the larger group characterized by an upregulation of inflammatory signaling predicted to promote pulmonary vascular remodeling. Both CD4+ and CD8+ T cells were identified and likely contribute to chronic inflammation in CTEPH. Smooth muscle cells were a heterogeneous population, with a cluster of myofibroblasts that express markers of fibrosis and are predicted to arise from other smooth muscle cell clusters based on pseudotime analysis. Lastly, our analysis identified protease-activated receptor 1 (PAR1) as a potential therapeutic target that links thrombosis to chronic PE in CTEPH

2023-02-07 | GSE224143 | GEO

Transcriptome sequencing and ceRNA (lncRNA-miRNA-mRNA) network construction identified the key molecular markers and signaling pathways of chronic thromboembolic pulmonary hypertension

Project description:For patients with chronic thromboembolic pulmonary hypertension (CTEPH), it can lead to death if left untreated. In this study, we attempted to identify key genes and pathways that could help in the diagnosis and treatment of CTEPH. It also provides research direction for further understanding the molecular mechanism of CTEPH.Firstly, we extract RNA from blood samples to construct the library. Then, qualified libraries were sequenced using PE100 strategy on BGIseq platform. Subsequently, the DESeq2 package in R was used to screen differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) of the CTEPH patient group and the normal control group. Afterwards, we performed functional enrichment and protein-protein interaction analysis of DEmRNAs. In addition, we also performed lncRNA-mRNA co-expression analysis and lncRNA-miRNA-mRNA network construction. A total of 437 DEmRNAs and 192 DElncRNAs were obtained. Subsequently, 205 pairs of interacting DEmRNAs and 232 pairs of lncRNA-mRNA relationship were obtained. Moreover, DEmRNAs were significantly enriched in chemokine signaling pathway, metabolic pathways, arachidonic acid metabolism and MAPK signaling pathway. In addition, only one regulation pathway of SOBP-has-miR-320b-LINC00472 was found through ceRNA network construction. In diagnostic analysis, the area under curve (AUC) of LINC00472, PIK3R6, SCN3A and TCL6 were greater than 0.7, which were 0.964, 0.893, 0.750 and 0.732, respectively. It is indicated that LINC00472, PIK3R6, SCN3A and TCL6 may as the potential diagnostic gene markers in CTEPH.

2022-08-17 | GSE188938 | GEO

Non-invasive approach for evaluation of CTEPH using extracellular vesicle-associated small non-coding RNA

Project description:The aim of this study was to determine whether extracellular vesicle (EV)-associated small non-coding RNAs (sncRNAs) have potential as biomarkers for chronic thromboembolic pulmonary hypertension (CTEPH). EVs were isolated using different methods from serum of 23 CTEPH patients and 23 controls. EV-associated RNAs were analysed by next-generation sequencing using the TrueQuant method for molecular barcoding, and differentially expressed sncRNAs were validated by qRT-PCR. We identified 18 miRNAs and 21 piRNAs or piRNA clusters that were differentially expressed in CTEPH patients compared with the control group. Bioinformatic analysis predicted a contribution of these piRNAs to the progression of cardiac and vascular remodelling. Furthermore, the expression levels of DQ593039 correlated with clinically meaningful parameters such as mean pulmonary arterial pressure, pulmonary vascular resistance, right ventricular systolic pressure, and levels of N-terminal pro-brain natriuretic peptide. In summary, EV-associated piRNA DQ593039 shows promise as biomarker and may be a potential therapeutic target for CTEPH.

2019-12-31 | GSE138107 | GEO

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