ArticleAmerican journal of respiratory and critical care medicine2015
Bone morphogenetic protein receptor type II deficiency and increased inflammatory cytokine production. A gateway to 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 95 papers, 2 of them syntheses that pooled it.
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Who cites it
95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 150 citations in OpenAlex.
- Impact of BMPR2 mutation on the severity of pulmonary arterial hypertension: a systematic review and meta-analysis.Respiratory research · 2025Pooled it
- Gender differences in pulmonary arterial hypertension patients with BMPR2 mutation: a meta-analysis.Respiratory research · 2020Pooled it
- 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
- Article
- Breast Cancer Reveals LatentCirculation · 2026Article
- Macrophage BMPRIB mediates p38-dependent inflammatory reprogramming and chemotaxis during ventilator-induced lung injury.Frontiers in immunology · 2026Article
- Endothelial glycosylation and its emerging role in pulmonary vascular health and disease.Nature communications · 2025Review
- Review of the British Thoracic Society Winter Meeting 2024.BMJ open respiratory research · 2025Article
- Porto-Pulmonary Hypertension and Hepato-Pulmonary Syndrome: Diagnostic Procedures and Therapeutic Management.Diagnostics (Basel, Switzerland) · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Interstitial Macrophages Drive Pulmonary Arteriole Medial Fibrosis in PAH.Circulation research · 2025Article
- Gut Microbiome in Pulmonary Arterial Hypertension-An Emerging Frontier.Infectious disease reports · 2025Review
- The sonic hedgehog signaling inhibitor cyclopamine improves pulmonary arterial hypertension via regulating the bone morphogenetic protein receptor 2 pathway.Scientific reports · 2025Article
- A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway.Nature cancer · 2025Article
- Loss of Type 2 Bone Morphogenetic Protein Receptor Activates NOD-Like Receptor Family Protein 3/Gasdermin E-Mediated Pyroptosis in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2025Article
- Gut Microbiome and Pulmonary Arterial Hypertension - A Novel and Evolving Paradigm.Physiological research · 2024Review
- Pulmonary Hypertension: Pharmacological and Non-Pharmacological Therapies.Life (Basel, Switzerland) · 2024Review
- Pulmonary Hypertension Induced by Right Pulmonary Artery Occlusion: Hemodynamic Consequences ofJournal of the American Heart Association · 2024Article
- Ethanol-induced lung and cardiac right ventricular inflammation and remodeling underlie progression to pulmonary arterial hypertension.Alcohol, clinical & experimental research · 2024Article
- Bone morphogenetic protein signalling in pulmonary arterial hypertension: revisiting the BMPRII connection.Biochemical Society transactions · 2024Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleMutations in bone morphogenetic protein receptor type II (BMPR-II) underlie most cases of heritable pulmonary arterial hypertension (PAH). However, disease penetrance is only 20-30%, suggesting a requirement for additional triggers. Inflammation is emerging as a key disease-related factor in PAH, but to date there is no clear mechanism linking BMPR-II deficiency and inflammation.
objectivesTo establish a direct link between BMPR-II deficiency, a consequentially heightened inflammatory response, and development of PAH.
methodsWe used pulmonary artery smooth muscle cells from Bmpr2(+/-) mice and patients with BMPR2 mutations and compared them with wild-type controls. For the in vivo model, we used mice heterozygous for a null allele in Bmpr2 (Bmpr2(+/-)) and wild-type littermates. MEASUREMENTS AND MAIN
resultsAcute exposure to LPS increased lung and circulating IL-6 and KC (IL-8 analog) levels in Bmpr2(+/-) mice to a greater extent than in wild-type controls. Similarly, pulmonary artery smooth muscle cells from Bmpr2(+/-) mice and patients with BMPR2 mutations produced higher levels of IL-6 and KC/IL-8 after lipopolysaccharide stimulation compared with controls. BMPR-II deficiency in mouse and human pulmonary artery smooth muscle cells was associated with increased phospho-STAT3 and loss of extracellular superoxide dismutase. Chronic lipopolysaccharide administration caused pulmonary hypertension in Bmpr2(+/-) mice but not in wild-type littermates. Coadministration of tempol, a superoxide dismutase mimetic, ameliorated the exaggerated inflammatory response and prevented development of PAH.
conclusionsThis study demonstrates that BMPR-II deficiency promotes an exaggerated inflammatory response in vitro and in vivo, which can instigate development of pulmonary hypertension.
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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.