Project description:To investigate the underlying mechanism of pulmonary hypertension, the model of monocrotaline (MCT)-treated pulmonary arterial hypertension (PAH) rats were constructed to detect the differentially expressed profile of genes in lung tissue of PAH rat.
Project description:To investigate the underlying mechanism of pulmonary hypertension, the model of monocrotaline (MCT)-treated pulmonary arterial hypertension (PAH) rats were constructed to detect the differentially expressed profile of circRNAs in lung tissue of PAH rat. The whole genome microarray expression profiling analysis as a discovery platform have been employed to identify genes difference.
Project description:Pulmonary arterial hypertension (PAH) is characterized by remodelling of the pulmonary arteries and right ventricle (RV), which leads to functional decline of cardiac and skeletal muscle. This study investigated the effects of a multi-targeted nutritional intervention with extra protein, leucine, fish oil and oligosaccharides on cardiac and skeletal muscle in PAH. PAH was induced in female C57BL/6 mice by weekly injections of monocrotaline (MCT) for 8 weeks. Control diet (sham and MCT group) and isocaloric nutritional intervention (MCT + NI) were administered. Compared to sham, MCT mice increased heart weight by 7%, RV thickness by 13% and fibrosis by 60% (all p < 0.05) and these were attenuated in MCT + NI mice. Microarray and qRT-PCR analysis of RV confirmed effects on fibrotic pathways. Skeletal muscle fiber atrophy was induced (P < 0.05) by 22% in MCT compared to sham mice, but prevented in MCT + NI group. Our findings show that a multi-targeted nutritional intervention attenuated detrimental alterations to both cardiac and skeletal muscle in a mouse model of PAH, which provides directions for future therapeutic strategies targeting functional decline of both tissues.
Project description:Investigated the expression profile and potential roles of mRNA and long non-coding RNAs (lncRNAs) in pulmonary arterial hypertension (PAH) mice induced by monocrotaline.
Project description:<p>Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, most studies have focused on the bacterial community and the exact role and mechanisms of multi-kingdom gut microbiota, including bacteria, archaea and fungi in PAH remains largely unclear. Idiopathic PAH (IPAH) patients exhibited distinct gut microbiota profiles with altered bacterial, archaeal and fungal compositions compared to healthy controls. Fecal microbiota transplantation (FMT) from IPAH patients or monocrotaline (MCT)-induced PAH rats to antibiotic treated rats induced PAH phenotypes, including increased right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling. Conversely, FMT from normal rats to MCT-PAH rats ameliorated PAH symptoms and reversed multi-kingdom gut microbiota dysbiosis. Metabolomics revealed significant alterations in plasma metabolites. Our findings established a causal link between multi-kingdom gut microbiota dysbiosis and PAH, demonstrating the therapeutic potential of FMT in reversing PAH phenotypes. More importantly, in addition to gut bacteria, gut archaeal and fungal communities also significantly correlate with PAH pathogenesis, highlighting their indispensable role in the gut.</p>
Project description:We studied the ability of the non-steroidal Mineralocorticoid Receptor (MR) antagonist finerenone to attenuate vascular remodeling and pulmonary hypertension (PH) using two complementary preclinical models [the monocrotaline (MCT) and Sugen
Project description:Inflammation and immunity play a causal role in the pathogenesis of pulmonary vascular remodeling and pulmonary arterial hypertension (PAH). However, the pathways and mechanisms by which inflammation and immunity contribute to pulmonary vascular remodeling remain unknown. RNA sequencing was used to analyze the transcriptome in control and rats injected with monocrotaline (MCT) for 1, 2, 3 and 4 weeks. Using the transcriptional profiling of MCT-induced PAH coupled with bioinformatics analysis, we clustered the differentially expressed genes (DEGs) and chose the increased expression patterns associated with inflammatory and immune response. We found the enrichment of Toll-like receptor (TLR) and NOD-like receptor (NLR) pathways and identified NF-κB-mediated inflammatory and immune profiling in MCT-induced PAH. Pathway-based data integration and visualization showed the dysregulated TLR and NLR pathways, including increased expression of TLR2 and NLRP3, and their downstream molecules. Further analysis revealed that the activation of TLR and NLR pathways was associated with upregulation of damage-associated molecular patterns (DAMPs) and RIPK3-mediated necroptosis was involved in the generation of DAMPs in MCT-induced PAH. Collectively, we identify RIPK3-mediated necroptosis and its triggered TLR and NLR pathways in the progression of pulmonary vascular remodeling, thus, providing novel insights into the mechanisms underlying inflammation and immunity in the pathogenesis of PAH.
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.
Project description:To investigate the genes associated with the progression pulmonary arterial hypertension，lung tissues of rats treated either with PBS buffer or monocrotaline (50mg/kg）were harvested for RNA-sequencing.
