ArticleThe Journal of experimental medicine2014
Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Meta-analysis of blood genome-wide expression profiling studies in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2020Pooled it
- From nanotechnology to immunomodulation: emerging strategies targeting macrophages in high altitude pulmonary hypertension.Journal of nanobiotechnology · 2026Review
- Case Report: Pulmonary artery biopsy findings in a patient with a BMPR2 variant-associated pulmonary arterial hypertension.Frontiers in medicine · 2026Article
- Circular RNA Profiling IdentifiesArteriosclerosis, thrombosis, and vascular biology · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Altered maturation and activation state of circulating monocytes is associated with their enhanced recruitment in pulmonary arterial hypertension.Respiratory research · 2025Article
- Microbiome-Immune Interaction in Pulmonary Arterial Hypertension: What Have We Missed?Research (Washington, D.C.) · 2025Review
- Therapeutic challenges and new therapeutic targets for combined capillary pulmonary hypertension: a review.Frontiers in medicine · 2025Review
- Mast Cells Contribute to Pressure Overload-Induced Myocardial Hypertrophy by Upregulating TRPV4 via Histamine: Role of Ca2+/ CnA/NFATc3 Signaling Pathway.Current medical science · 2024Article
- Pulmonary Hypertension: Pharmacological and Non-Pharmacological Therapies.Life (Basel, Switzerland) · 2024Review
- Empagliflozin Attenuates Pulmonary Arterial Remodeling Through Peroxisome Proliferator-Activated Receptor Gamma Activation.ACS pharmacology & translational science · 2024Article
- Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension.Respiratory research · 2024Review
- Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy.American journal of respiratory and critical care medicine · 2024Article
- The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications.Frontiers in immunology · 2024Review
- Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension.Nature communications · 2023Article
- Pharmacology and Rationale for Seralutinib in the Treatment of Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- Eosinophils protect against pulmonary hypertension through 14-HDHA and 17-HDHA.The European respiratory journal · 2023Article
- Disruption of GCN2 Pathway Aggravates Vascular and Parenchymal Remodeling during Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2023Article
- Novel Molecular Mechanisms Involved in the Medical Treatment of Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.Frontiers in immunology · 2023Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 enhances production of the potent chemokine granulocyte macrophage colony-stimulating factor (GM-CSF) in response to an inflammatory perturbation. When human pulmonary artery (PA) endothelial cells deficient in BMPR2 were stimulated with tumor necrosis factor (TNF), a twofold increase in GM-CSF was observed and related to enhanced messenger RNA (mRNA) translation. The mechanism was associated with disruption of stress granule formation. Specifically, loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34-PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2α), and derepressing GM-CSF mRNA translation. Lungs from IPAH patients versus unused donor controls revealed heightened PA expression of GM-CSF co-distributing with increased TNF and expanded populations of hematopoietic and endothelial GM-CSF receptor α (GM-CSFRα)-positive cells. Moreover, a 3-wk infusion of GM-CSF in mice increased hypoxia-induced PAH, in association with increased perivascular macrophages and muscularized distal arteries, whereas blockade of GM-CSF repressed these features. Thus, reduced BMPR2 can subvert a stress granule response, heighten GM-CSF mRNA translation, increase inflammatory cell recruitment, and exacerbate PAH.
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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.