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Hypoxia-induced pulmonary hypertension in calf right ventricle

ABSTRACT: Hypoxia-induced pulmonary hypertension in calf right ventricle

PROVIDER: PRJNA899456 | ENA |

REPOSITORIES: ENA

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Hypoxia-induced pulmonary hypertension in calf right ventricle

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

Heart ventricles proteomic profile in pulmonary arterial hypertension

Project description:Arterial pulmonary hypertension is a rare disease, with little knowledge regarding its etiology, and high mortality. Development of right and later on also left ventricular heart insufficiency, secondary to pulmonary hypertension, is a negative predictive factor. Genetic and molecular processes underlying left heart ventricle remodeling over the course of pulmonary hypertension remain unknown. In particular, there is no knowledge regarding the mechanisms of left heart ventricle atrophy which was completely avoided by researchers until recently.The aim of this study was to assess changes in protein abundance in left and right heart ventricle free wall of rats in monocrotaline model of PAH.

2020-09-07 | PXD015896 | Pride

Characterization of DNA methylation changes associated with lung and right ventricle dysfunction in pulmonary hypertension

Project description:Characterization of DNA methylation changes associated with lung and right ventricle dysfunction in pulmonary hypertension

| PRJNA860188 | ENA

Characterization of DNA methylation changes associated with lung and right ventricle dysfunction in pulmonary hypertension

Project description:Pulmonary arterial hypertension (PAH) is a lethal vasculopathy associated with pulmonary arteries remodeling and right ventricle (RV) dysfunction. Epigenetic dysregulation, including altered DNA methylation, promotes PAH. However, the DNA methylation changes associated with PAH and their functional consequences on transcriptomic reprogramming remain unexplored in human PAH RV and lungs. We conducted an exploratory study in human lung and RV samples to characterize the DNA methylome and transcriptomic changes associated with PAH in both organs. Impaired DNA methylation landscape observed in PAH lungs and RV correlates with adverse pulmonary vascular remodeling, RV fibrosis, and markers of disease severity (e.g. NT-proBNP). PAH differentially methylated genes and differentially expressed transcripts regulate biological functions related to inflammation, fibrosis, heart contraction, blood vessel development. Moreover, we observed substantial lung/RV transcriptomic and methylomic changes overlap in PAH. Thus, PAH is associated with specific DNA methylation changes associated with the disease severity.

2024-12-01 | GSE208592 | GEO

Gene expression in rat right ventricles during chronic pulmonary embolism

Project description:Pulmonary vascular occlusions due to thromboemboli can result in pulmonary hypertension and right heart damage. Treatments to clear the vascular obstructions such as i.v. heparain or thrombolytics can resolve the hypertension but right ventricular damage often occurs first. Methods of protecting the right ventricle from hypertensive damage during the course of acute treatment to clear the thromboemboli are needed. Monocyte- and neutrophil-mediated inflammation and fibrosis are associated with chronic right ventricular damage but the pathways involved are not understood. A comprehesive survey of gene expression during chronic pulmonary embolism verses control rats has been conducted in this study.

2009-09-01 | GSE11851 | 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

Hypoxia Induced Pulmonary Hypertension

Project description:Here we investigated the protein composition of the main pulmonary artery (MPA), distal pulmonary arteries (DPA) distal whole lung (DWL) of early stage hypoxia (using a neonatal bovine calf model) and late stage hypoxia (using adult steers with hypoxia-induced PH) using high resolution mass spectrometry. Compartment-resolved analysis allowed for quantitative measurements of proteins from cellular, soluble ECM and insoluble ECM fractions

2022-10-06 | MSV000090482 | MassIVE

Expression data from human heart right ventricular wall

Project description:Gene expression in the right ventricle is different in control patients as compared to either idiopathic dilated cardiomyopathy or pulmonary arterial hypertension Two human hearts obtained at autopsy from each of control, pulmonary hypertension, and dilated cardiomyopathy

2015-04-02 | E-GEOD-67492 | biostudies-arrayexpress

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

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