Project description:Pulmonary veno-occlusive disease (PVOD) is characterized by increased pulmonary vascular resistance. Currently, there is a lack of effective treatment. It is of great significance to explore molecular targets for treatment of the disease. This study investigated the differentially expressed profile of miRNAs and tight junction in the lung tissue of rats with mitomycin-C induced PVOD.
Project description:Pulmonary endothelial dysfunction plays an integral role in mediating the initiation and progression of pulmonary vascular remodelling, an important feature of pulmonary arterial hypertension (PAH). Our aim was to decipher the gene expression program of endothelial cells derived from circulating endothelial progenitor (EPCs) to gain insight into the pathological process of PAH associated with systemic sclerosis (SSc), which is the most extreme vascular phenotype of this disease. We used microarrays to investigate the gene expression profile in late outgrowth EPC-derived endothelial cells issued from SSc-PAH patients, in comparison with SSc patients without PAH and healthy controls.
Project description:Aging is a risk factor for many non-communicable diseases such as cardiovascular and neurodegenerative diseases. Aging could impact the extracellular vesicles and particles (EVPs) miRNA profile and impair redox homeostasis, contributing to chronic age-related diseases. We aimed to investigate the microRNA profiles of circulating total EVPs from aged and young adult animals. Plasma from 3- and 21-month-old male Wistar rats was collected and circulating total EVPs were isolated. MicroRNA isolation and microarray expression analysis were performed on EVPs to determine the predicted regulation of targeted mRNAs. 31 mature miRNAs in circulating EVPs were impacted by age and predicted to target molecules in canonical pathways directly related to cardiovascular diseases and oxidative status. Our data show that circulating total EVP cargo, specifically microRNAs, are involved in redox imbalance in the aging process and can potentially drive cardiovascular aging and consequently cardiac disease.
Project description:One current concept suggests that unchecked proliferation of clonally selected precursors of endothelial cells contribute to severe pulmonary arterial hypertension (pAH). We hypothesized that clonally selected ECs expressing the progenitor marker CD117 promote severe occlusive pulmonary hypertension (PH). We used microarrays to identify the steady state gene expression profile of quaternary clones derived from CD117+ rat lung ECs vs control ECs derived from rat lung CD117- cells.
Project description:IL-4-mediated pro-inflammatory vascular responses have been implicated in the pathogenesis of chronic cardiopulmonary diseases. Our results show that hypoxia-induced collagen synthesis and early recruitment of inflammatory cells are significantly less in the lungs of IL-4 knockout (KO) mice than in those of wild-type mice. In addition, we found that IL-4 significantly increased pro-inflammatory genes in primary pulmonary microvascular endothelial cells. This study was designed to identify the gene expression profile of IL-4-dependent pulmonary vascular inflammation induced by hypoxia.
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). Our objective was to profile and analyze the differential gene expression signatures between the cells isolated from normal and idiopathic PAH patients. We generated vascular cell-specific transcriptome profiles from the adventitial fibroblasts (PAAF) isolated ex vivo from the dissected human pulmonary arteries of normal donor and PAH lungs using paired-end RNA-sequencing.
Project description:This study was designed to investigate the global gene expression of circulating, prodomain bound form of BMP9 (pro-BMP9) in human pulmonary arterial endothelial cells (PAECs) because previous microarray experients have used the growth factor domain alone. We are interested in its signalling capacity in pulmonary vascular endothelial cells using the physiological circulating form and at physiologically circulating concentrations. Also, this study reports data 5 hours after the treatment to look at the secondary genes regulated by BMP9 signalling.
Project description:Pulmonary arterial hypertension (PAH) is a progressive disorder leading to occlusive vascular remodeling. Current PAH therapies improve quality of life but do not reverse structural abnormalities in the pulmonary vasculature. Here, we used a high-throughput drug screen combined with in silico analyses of existing transcriptomic datasets to identify a promising lead compound to reverse PAH. Induced pluripotent stem cell-derived endothelial cells (iPSC-EC) generated from six patients with PAH were exposed to 4,500 compounds and assayed for improved cell survival after serum withdrawal using a chemiluminescent caspase assay. Subsequent validation of caspase activity and improved angiogenesis combined with in silico analyses using the Gene Expression Omnibus (GEO ) and Library of Integrated Network-Based Cellular Signatures (LINCS) databases revealed that the lead compound AG1296 was positively associated with an anti-PAH gene signature. AG1296 increased abundance of bone morphogenetic protein receptors (BMPR2 and Ia), downstream signaling and gene expression, and suppressed PAH smooth muscle cell proliferation. AG1296 induced regression of pulmonary arterial (PA) neointimal lesions in lung organ culture and PA occlusive changes in the Sugen/hypoxia rat model and reduced right ventricular systolic pressure. Moreover, AG1296 improved vascular function and BMPR2 signaling and showed better correlation with the anti-PAH gene signature than other tyrosine kinase inhibitors (TKIs) such as imatinib. Specifically, AG1296 upregulated the transcription factors and small mothers against decapentaplegic (SMAD)1/5 co-activators, cAMP-response element binding protein (CREB)3 and CREB5: CREB3 induced inhibitor of DNA binding 1 (ID1) and downstream genes that improved vascular function. Thus, drug discovery for PAH can be accelerated by combining a phenotypic screen using patient-specific iPSC-derived vascular cells with in silico analyses of publicly available datasets.
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). Our objective was to profile and analyze the differential gene expression signatures between the cells isolated from normal and idiopathic PAH patients. We generated vascular cell-specific transcriptome profiles from the adventitial fibroblasts (PAAF) isolated ex vivo from the dissected human pulmonary arteries of normal donor and PAH lungs using paired-end RNA-sequencing.
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). Our objective was to profile and analyze the differential gene expression signatures between the cells isolated from normal and idiopathic PAH patients. We generated vascular cell-specific transcriptome profiles from the adventitial fibroblasts (PAAF) isolated ex vivo from the dissected human pulmonary arteries of normal donor and PAH lungs using paired-end RNA-sequencing.
