A Potential Diagnostic Biomarker in Pulmonary Hypertension
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE215341 | GEO | 2022/10/14
REPOSITORIES: GEO
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Project description:Pulmonary hypertension (PH) is a life-threatening disease, characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary arterial pressure and right heart hypertrophy. PH is caused, among other factors, by chronic hypoxia, leading to hyper-proliferation of pulmonary arterial smooth muscle cells (PASMC) and apoptosis-resistant pulmonary microvascular endothelial cells (PMVEC). Upon re-exposure to normoxia, chronic hypoxia-induced PH in mice is reversible. In this study, we aim to identify novel candidate genes involved in pulmonary vascular remodeling specifically in the pulmonary vasculature.
2022-09-01 | GSE183908 | GEO
Project description:A porcine microarray study of right ventricular failure due to coronary artery ligation of the right ventricular free wall and subsequent treatment of right ventricular failure by volume unloading using a shunt between superior vena cava and the pulmonary artery (Glenn-shunt) 1. Surgical preparation with a 12 mm graft between superior vena cava and pulmonary artery, the graft is then clamped - Baseline sample using a biopsy needle. 2. After surgical preparation the coronary arteries of the right ventricular free wall are ligated, then heart failure develops over 120 minutes - Failure sample using a biopsy needle. 3. The shunt is then opened and the superior vena cava closed between the shunt and right atrium, diverting the blood from superior vena cava through the shunt for a period of 15 minutes partially unloading the right ventricle - Shunt sample using a biopsy needle. A series of six pigs, three samples from each animal: baseline, failure and shunt/treatment.
2011-08-23 | E-GEOD-31619 | biostudies-arrayexpress
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:The molecular mechanisms of progressive right heart failure are incompletely understood. We systematically examined transcriptomic changes occurring over months in isolated cardiomyocytes or whole heart tissues from failing right and left ventricles in rat models of pulmonary artery (PAB) or aortic banding (AOB). Detailed bioinformatics analyses resulted in the identification of gene signatures, protein, and transcription factor networks specific to ventricles and compensated or decompensated disease states. Proteomic and RNA-FISH analyses confirmed PAB-mediated regulation of key genes (including proenkephalin) and revealed spatially heterogeneous mRNA expression in the heart. Intersection of rat PAB-specific gene sets with transcriptome data sets from human patients with chronic thromboembolic pulmonary hypertension led to the identification of more than 50 genes whose expression levels correlated with the severity of right heart disease, including multiple matrix-regulating and secreted factors. These data define a conserved, differentially regulated genetic network associated with right heart failure in rats and humans
2024-04-11 | PXD047022 | Pride
Project description:We hypothesize that transpulmonary metabolomic profiling will demonstrate a PAH-specific metabolic signature. We will examine organ-specific metabolism by measuring blood flowing into (pulmonary artery) and out of (pulmonary artery wedge) the pulmonary circulation at the time of right heart catheterization (RHC). We will compare PAH to patients without PH and to a disease control cohort with PH due to left heart disease (pulmonary ventrical hypertension - PVH).
2016-09-07 | ST000464 | MetabolomicsWorkbench
Project description:Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that culminates in right heart failure. Vascular pathology in PH is characterized by pulmonary vasoconstriction and progressive vascular remodeling processes that affects all layers of the vascular wall (intima, media and adventitia).
2022-06-09 | GSE194080 | GEO
Project description:Pulmonary hypertension (PH) is an incurable right heart failure disease. Parathyroid hormone (PTH) is secreted from the parathyroid gland and plays a crucial role in calcium homeostasis. PTH also acts on the cardiovascular system and affects cardiovascular prognosis. We assessed whether the regulation of PTH affected PH in a hypoxia (Hx)-induced PH mouse model. PTH treatment exacerbated right ventricular hypertrophy and right ventricular systolic pressure in Hx mice. Our data showed how is PTH effected for PH model murine lung.
2023-10-11 | GSE244861 | GEO
Project description:Rationale: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Objectives: To determine whether upregulation of fatty-acid binding protein 4 and 5 (FABP4/5) is critical in pathogenesis of PAH. Methods: FABP4/5 expression was examined in pulmonary arterial endothelial cells (PAECs) and lung tissues from patients with idiopathic PAH and pulmonary hypertension (PH) rat models. Plasma proteome analysis was performed in human PAH samples. Echocardiography, hemodynamics, histology, and immunostaining were performed to evaluate the lung and heart PH phenotypes in Egln1Tie2Cre (CKO) mice and Egln1Tie2Cre/Fabp4-5-/- (TKO) mice. Measurement and Main Results: Both FABP4 and FABP5 were highly induced in ECs of CKO mice and PAECs from IPAH patients, and in whole lungs of PH rats. Plasma levels of FABP4/5 were upregulated in IPAH patients and directly correlated with severity of hemodynamics and biochemical parameters. Genetic deletion of both Fabp4 and 5 in CKO mice caused a reduction of right ventricular systolic pressure (RVSP) and RV hypertrophy, attenuated pulmonary vascular remodeling and prevented the right heart failure. Fabp4/5 deletion also normalized EC glycolysis, reduced ROS and HIF-2a expression, and decreased aberrant EC proliferation in CKO lungs. Conclusions: PH causes aberrant expression of FABP4/5 in pulmonary ECs which leads to enhanced EC glycolysis and hyperproliferation, contributing to the accumulation of arterial ECs and vascular remodeling and exacerbating the disease.
2024-08-02 | GSE261445 | GEO
Project description:Heart failure is among the leading causes of death globally. Ventricular failure progresses through a hypertrophic compensatory phase followed by failure of the ventricle function through rapid decompensation. In order to unravel right heart specific mechanisms of disease, rat animal models were established that (i) reflect the slowly progressive mode of compensation / decompensation and (ii) allow comparative analyses of left versus right heart failure in the same experimental set up. Non-restrictive clips around the pulmonary artery (pulmonary artery banding, PAB) or the aorta (aortic banding, AOB) were surgically implanted into weanling rats. Upon animal growth the clips become increasingly constrictive, leading to a compensatory, hypertrophic state at around 6 weeks and heart failure at 21 (PAB) or 24 weeks (AOB). Disease progression was monitored functionally and by sonography. Differential gene expression analysis was performed for all three treatment groups (sham, AOB, PAB), at both time points (compensation, decompensation) and for both ventricles.
2024-04-15 | GSE216263 | GEO
