Digital Spatial Profiling identifies distinct molecular signatures of vascular lesions in Pulmonary Arterial Hypertension
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ABSTRACT: Idiopathic Pulmonary Arterial Hypertension (IPAH) is a severe human disease, characterized by extensive pulmonary vascular remodeling due to plexiform and obliterative lesions, media hypertrophy, and alterations of adventitia. The objective of the study was to test the hypothesis that microscopic IPAH vascular lesions express unique molecular profiles, which collectively are different from control pulmonary arteries. We used digital spatial transcriptomics to profile the genome-wide differential transcriptomic signature of key pathological lesions (plexiform, obliterative, intima+media hypertrophy, and adventitia) in IPAH lungs (n= 11) and compared these data to the intima+media and adventitia of control pulmonary artery (n=5). The IPAH lesions and pulmonary artery compartments were defined by the analyses of hematoxylin-eosin stained serial section, aided by labeling with CD31 (for endothelial cells), smooth muscle cell actin (SMA), and CD45 for inflammatory mononuclear cells, also in serial sections. Approximately 12 regions of interest (ROI) were sampled from a histological section of a paraffin-embedded block of each lung, which was selected based on the finding of enrichment for IPAH lesions or control pulmonary arteries.
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.
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.
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).
Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a proliferative endothelial cell phenotype, inflammation and pulmonary vascular remodeling. BMPR2 loss-of-function has been linked to pathologic plexiform lesions with obliteration of distal pulmonary arteries distal pulmonary arteries BMPR2 silencing inprimary human pulmonary artery ECs (HPAECs) recapitulate important aspects of cellular dysfunction and deregulated signaling associated with PAH. Primary HPAECs were transfected with gene-specific siRNA pools targeting BMPR2 or control siRNA followed PMA or control stimulation.
Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a proliferative endothelial cell phenotype, inflammation and pulmonary vascular remodeling. BMPR2 loss-of-function has been linked to pathologic plexiform lesions with obliteration of distal pulmonary arteries distal pulmonary arteries BMPR2 silencing inprimary human pulmonary artery ECs (HPAECs) recapitulate important aspects of cellular dysfunction and deregulated signaling associated with PAH.
Project description:Samples surgically extracted from CTEPH pulmonary arteries were compared to post-transplant pulmonary arteries from IPAH and failed donor pulmonary arteries from controls The goal was to determine if altered gene expression in CTEPH associated with development of chronic thrombi