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Transcriptome profile of fibroblasts in chronic thromboembolic pulmonary hypertension

ABSTRACT: Transcriptome profile of fibroblasts in chronic thromboembolic pulmonary hypertension

PROVIDER: PRJNA628645 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11614730.fastq.gz	Fastqsanger.gz
	SRR11614731.fastq.gz	Fastqsanger.gz
	SRR11614732.fastq.gz	Fastqsanger.gz
	SRR11614733.fastq.gz	Fastqsanger.gz
	SRR11614734.fastq.gz	Fastqsanger.gz

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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.

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

Project description: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).

2024-04-18 | GSE249694 | 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

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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.

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2024-04-18 | GSE249696 | 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.

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

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