ArticleCirculation research2009
Interleukin-6 overexpression induces pulmonary hypertension.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 346 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
346 citing papers in PubMed, 2 syntheses or guidelines pooled it, 635 citations in OpenAlex.
- Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.Science translational medicine · 2024Pooled it
- Dose-related Effects of Resveratrol in Different Models of Pulmonary Arterial Hypertension: A Systematic Review.Current cardiology reviews · 2020Pooled it
- The ALPHA phase 1 study: pulmonary ArteriaL hypertension treated with CardiosPHere-Derived allogeneic stem cells.EBioMedicine · 2024Trial
- Trial
- Post-translational modification crosstalk in pulmonary arterial hypertension: mechanisms and therapeutic implications.Molecular biology reports · 2026Review
- Mesenchyme-derived inflammation during the saccular stage recruits macrophages and alters lung development.JCI insight · 2026Article
- Interleukin-6 is critical in the development of pulmonary vascular disease inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pulmonary hypertension associated with interstitial lung disease: a state-of-the-art review.The European respiratory journal · 2026Review
- Global Burden of Pulmonary Arterial Hypertension in Older Adults and Its Causal Association With Body Mass Index.Pulmonary circulation · 2026Article
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- Endothelial USP2a-METTL16 loop potentiates IL-6 signaling via mCell death and differentiation · 2026Article
- Reduction in microbiota-derived short-chain fatty acids contributes to the pathogenesis of pulmonary arterial hypertension.Respiratory research · 2026Article
- Deciphering the Counterintuitive Role of Vascular Endothelial Growth Factor Signaling Pathways in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2026Review
- Deficiency of Smooth Muscle Adar1 Exacerbates Vascular Remodeling and Pulmonary Hypertension.Circulation research · 2026Article
- Endothelial ADAR1 Deficit Induces the NOCT-IRF7 Axis in Pulmonary Hypertension.Circulation research · 2026Article
- Integrative single-cell RNA-seq and ATAC-seq analysis reveals the key role of inflammatory cell activation in pulmonary arterial hypertension.Frontiers in immunology · 2026Article
- Mouse models for post-sepsis syndrome: a comparison of cecal slurry injection model versus two cecal ligation and puncture models.Frontiers in medicine · 2026Article
- Targeting Pulmonary Hypertension: Elucidating Sophocarpine's Protective Role via Preclinical Models.Mediators of inflammation · 2026Article
- Advances in Novel Therapeutic Strategies for Pulmonary Arterial Hypertension.Canadian respiratory journal · 2026Review
- IL-6 and TGF-β1 as biomarkers of schistosomiasis-associated pulmonary hypertension in a murine model.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
286 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.