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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE249697 | 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 [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

2024-04-18 | GSE249691 | GEO

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

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

| PRJNA1050197 | ENA

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

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

| PRJNA1050201 | ENA

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

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

| PRJNA1050205 | ENA

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

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

| PRJNA1050207 | ENA

Reverse right ventricular structural and extracellular matrix remodeling by estrogen in severe pulmonary hypertension.

Project description:Chronic pulmonary hypertension (PH) leads to right-ventricular failure (RVF) characterized by RV remodeling. Ventricular remodeling is emerging as an important process during heart failure and recovery. Remodeling in RVF induced by PH is not fully understood. Recently we discovered that estrogen (E2) therapy can rescue severe preexisting PH. Here, we focused on whether E2 (42.5 μg·kg(-1)·day(-1), 10 days) can reverse adverse RV structural and extracellular matrix (ECM) remodeling induced by PH using monocrotaline (MCT, 60 mg/kg). RV fibrosis was evident in RVF males. Intact females developed less severe RV remodeling compared with males and ovariectomized (OVX) females. Novel ECM-degrading disintegrin-metalloproteinases ADAM15 and ADAM17 transcripts were elevated ∼2-fold in all RVF animals. E2 therapy reversed RV remodeling in all groups. In vitro, E2 directly inhibited ANG II-induced expression of fibrosis markers as well as the metalloproteinases in cultured cardiac fibroblasts. Estrogen receptor-β agonist diarylpropionitrile (DPN) but not estrogen receptor-α agonist 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) was as effective as E2 in inhibiting expression of these genes. Expression of ECM-interacting cardiac fetal-gene osteopontin (OPN) also increased ∼9-fold in RVF males. Intact females were partially protected from OPN upregulation (∼2-fold) but OVX females were not. E2 reversed OPN upregulation in all groups. Upregulation of OPN was also reversed in vitro by E2. Plasma OPN was elevated in RVF (∼1.5-fold) and decreased to control levels in the E2 group. RVF resulted in elevated Akt phosphorylation, but not ERK, in the RV, and E2 therapy restored Akt phosphorylation. In conclusion, E2 therapy reverses adverse RV remodeling associated with PH by reversing fibrosis and upregulation of novel ECM enzymes ADAM15, ADAM17, and OPN. These effects are likely mediated through estrogen receptor-β.

| S-EPMC3404831 | biostudies-literature

Prognostic Value of Pulmonary Artery Pulsatility Index in Right Ventricle Failure-Related Mortality in Inoperable Chronic Thromboembolic Pulmonary Hypertension.

Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is an ominous disease leading to progressive right ventricular failure (RVF) and death. There is no reliable risk stratification strategy for patients with CTEPH. The pulmonary artery pulsatility index (PAPI) is a novel hemodynamic index that predicts the occurrence RVF. We aimed to investigate prognostic value of PAPI in inoperable CTEPH. Consecutive patients with inoperable CTEPH were enrolled. PAPI was calculated from baseline right heart catheterization data. A prognostic cut-off value was determined, and characteristics of low- and high-PAPI groups were compared. The association between risk assessment and survival was also evaluated. We included 50 patients (mean age 64 ± 12.2 years, 60% female). The number of deaths was 12 (24%), and the mean follow-up time was 52 ± 19.3 months. The established prognostic cut-off value for PAPI was 3.9. The low-PAPI group had significantly higher mean values of mean atrial pressure (14.9 vs. 7.8, p = 0.0001), end-diastolic right ventricular pressure (16.5 vs. 11.2, p = 0.004), and diastolic pulmonary artery pressure (35.8 vs. 27.7, p = 0.0012). The low-PAPI group had lower survival as compared to high-PAPI (log-rank p < 0.0001). PAPI was independently associated with survival and may be applicable for risk stratification in inoperable CTEPH.

| S-EPMC9147458 | biostudies-literature

Myocardial Fibrosis as a Potential Maladaptive Feature of Right Ventricle Remodeling in Pulmonary Hypertension.

Project description: Not available

| S-EPMC6775878 | biostudies-literature