Project description:In dogs with degenerative mitral valve disease (DMVD), pulmonary hypertension (PH) is a common complication characterized by abnormally elevated pulmonary arterial pressure (PAP). Pulmonary arterial remodeling is the histopathological changes of pulmonary artery that has been recognized in PH. The underlying mechanisms that cause this arterial remodeling are poorly understood. This study aimed to perform shotgun proteomics to investigate changes in protein expression in pulmonary arteries and lung tissues of DMVD dogs with PH compared to normal control dogs and DMVD dogs without PH.
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:Gut Microbiota Alterations in Fontan Patients with Elevated Pulmonary Arterial Pressure
Project description:Pulmonary arterial hypertension (PAH) is a progressive disease marked by pulmonary vascular remodeling, elevated pulmonary pressures, and right ventricular (RV) failure. In this study, a sugen-hypoxia rat model of PAH was used to evaluate a novel, degradation-resistant apelin analog targeting the apelinergic pathway, which is implicated in pulmonary vascular remodeling. Treatment with the apelin analog reversed key pathological features of PAH, including pulmonary vascular lesions, elevated pulmonary arterial pressures, RV dilation and dysfunction, and early cardiorenal syndrome. The therapy also reduced RV cardiomyocyte and fibroblast activation caused by pressure overload. Single-nucleus RNA sequencing of the lungs and RV demonstrated that apelin analog treatment activated protective molecular programs, notably restoring balance between protective BMPR2 signaling and pathogenic TGFBR2 signaling. Overall, these findings suggest that exogenous apelin therapy may represent a promising strategy to reverse pulmonary vascular and cardiac remodeling in PAH and warrants further clinical investigation.
Project description:Pulmonary arterial hypertension (PAH) is characterized by severe obstruction of small pulmonary arteries and concomitant high pulmonary arterial pressure, resulting in progressive right ventricular failure. Previously, we demonstrated that long-term interleukin (IL)-33 administration in mice induced severe occlusive arterial hypertrophy in the lung, which was mediated by group 2 innate lymphoid cells (ILC2s). In response to IL-33, ILC2s accumulated around blood vessels and produced IL-5, leading to perivascular eosinophil recruitment. In this study, we further characterized IL-33-induced pulmonary arterial hypertrophy. We first demonstrated that long-term IL-33 administration caused an increase in the right ventricular pressure. In IL-33 deficient mice, pulmonary arterial hypertrophy mediated by eggs of Schistosoma mansoni (S. mansoni) was attenuated, accompanied with partial reduction in ILC2s, eosinophils and CD4+ T cells. In addition, proteomic analysis revealed dramatic changes in urine samples from mice treated with IL-33 or S. mansoni eggs. Resistin like alpha (RELM), a pulmonary hypertension-related molecule, in the urine was commonly detected in both treatments. Large amounts of RELM were observed in the lung from IL-33-treated mice. These observations support that IL-33-induced pulmonary arterial hypertrophy is a useful model to study the mechanism underlying development of PAH and expolar biomarkers to indicate the onset of PAH.
Project description:It has been reported that repeated intra-tracheal instillation of S. chartarum spores induced significant pulmonary arterial remodeling in mice, which resulted in pathological changes like human pulmonary arterial hypertension (PAH) and elevation right ventricle systolic pressure. Then, we used microarrays to know the complex molecular mechanisms that underlie pathogenesis of PAH.
Project description:Pulmonary hypertension (PH) encompasses a diverse spectrum of disorders characterized by elevated pulmonary arterial pressure presenting substantial morbidity and mortality challenges. Despite significant advancements in understanding its underlying pathophysiology therapeutic options remain limited particularly in cases where patients exhibit elevated pulmonary pressures despite maintaining a preserved left ventricular ejection fraction. The traditional focus on right ventricular (RV) function in PH has led to the underestimation of the impact on the left ventricle (LV) due to the absence of high-resolution modalities capable of monitoring the electromechanical coupling in both ventricles. We present here the results of an integrated histology and transcriptome analysis used to improve our understanding of the pathophysiology of pulmonary hypertension and identify the different molecular responses due to MCT-induced PH.
Project description:Epigenetic modifications have been shown to be important in developmental tumors as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors and 7 cell lines using the Infinium Human Methylation 450k. Differential methylation analysis between Ewing sarcoma and reference samples revealed 1,166 hypermethylated and 864 hypomethylated CpG sites (Bonferroni p<0.05, δ-β-value with absolute difference of >0.20) corresponding to 392 and 470 genes respectively. Gene Ontology analysis of genes differentially methylated in Ewing sarcoma samples showed a significant enrichment of developmental genes. Membrane and cell signal genes were also enriched, among those, 11 were related to caveola formation. We identified differential hypermethylation of CpGs located in the body and S-Shore of the PTRF gene in Ewing sarcoma that correlated with its repressed transcriptional state. Reintroduction of PTRF/Cavin-1 in Ewing sarcoma cells revealed a role of this protein as a tumor suppressor. Restoration of caveolae in the membrane of Ewing sarcoma cells, by exogenously reintroducing PTRF, disrupts the MDM2/p53 complex, which consequently results in the activation of p53 and the induction of apoptosis.
