ArticleAmerican journal of respiratory and critical care medicine2015
RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension.
Article in American journal of respiratory and critical care medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 84 citations in OpenAlex.
- Proteogenomic Profiling of Idiopathic Pulmonary Arterial Hypertension Identifies Sex-Differential Proteins and Candidate Therapeutic Targets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- KLF6 activation marks an angiogenic and apoptosis resistant endothelial phenotype in pulmonary arterial hypertension.Communications biology · 2026Article
- Experimental pulmonary arterial hypertension in mice with a pathogenic SOX17 variant.Scientific reports · 2026Article
- Long non-coding RNA LINC00607 epigenetically regulates endothelial TSPAN18 to promote hypoxia-induced thromboinflammation.The Journal of biological chemistry · 2026Article
- Novel Insights Into Receptor Tyrosine Kinases in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2025Review
- Pressure Points: Endothelial Responses to Shear Stress and Pressure in Health and Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2025Article
- Beyond classical collagen: basement membrane collagen IV in age-associated lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Enhanced lung endothelial glycolysis is implicated in the development of severe pulmonary hypertension in type 2 diabetes.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- Digital Spatial Profiling Identifies Distinct Molecular Signatures of Vascular Lesions in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2024Article
- Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension.Scientific reports · 2023Article
- Biomarkers in Pulmonary Arterial Hypertension.Diagnostics (Basel, Switzerland) · 2022Review
- An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis.Communications biology · 2022Article
- Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertension.Life science alliance · 2022Article
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- Heat shock protein 70 attenuates hypoxia‑induced apoptosis of pulmonary microvascular endothelial cells isolated from neonatal rats.Molecular medicine reports · 2021Article
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- NEDD9 Is a Novel and Modifiable Mediator of Platelet-Endothelial Adhesion in the Pulmonary Circulation.American journal of respiratory and critical care medicine · 2021Article
- ALDH1A3 Coordinates Metabolism With Gene Regulation in Pulmonary Arterial Hypertension.Circulation · 2021Article
- iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension.Science translational medicine · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 1 institution in 2 countries.
Funding
Abstract
rationalePulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function.
objectivesRNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess the functional significance of major differentially expressed transcripts.
methodsThe endothelial transcriptomes from the lungs of seven control subjects and six patients with idiopathic pulmonary arterial hypertension were analyzed. Differentially expressed genes were related to bone morphogenetic protein type 2 receptor (BMPR2) signaling. Those down-regulated were assessed for function in cultured cells and in a transgenic mouse. MEASUREMENTS AND MAIN
resultsFold differences in 10 genes were significant (P < 0.05), four increased and six decreased in patients versus control subjects. No patient was mutant for BMPR2. However, knockdown of BMPR2 by siRNA in control pulmonary arterial endothelial cells recapitulated 6 of 10 patient-related gene changes, including decreased collagen IV (COL4A1, COL4A2) and ephrinA1 (EFNA1). Reduction of BMPR2-regulated transcripts was related to decreased β-catenin. Reducing COL4A1, COL4A2, and EFNA1 by siRNA inhibited pulmonary endothelial adhesion, migration, and tube formation. In mice null for the EFNA1 receptor, EphA2, versus control animals, vascular endothelial growth factor receptor blockade and hypoxia caused more severe pulmonary hypertension, judged by elevated right ventricular systolic pressure, right ventricular hypertrophy, and loss of small arteries.
conclusionsThe novel relationship between BMPR2 dysfunction and reduced expression of endothelial COL4 and EFNA1 may underlie vulnerability to injury in pulmonary arterial hypertension.
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