ArticleNature communications2021
An endothelial activin A-bone morphogenetic protein receptor type 2 link is overdriven in pulmonary hypertension.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Efficacy and safety of sotatercept in pulmonary arterial hypertension: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Pooled it
- Artificial Intelligence and Multi-Omics Approaches in the Precision Management of Pulmonary Hypertension: From Early Diagnosis to Therapeutic Stratification.International journal of molecular sciences · 2026Review
- Navigating the Complexity of PH-ILD: From Molecular Mechanisms to Integrated Clinical Evaluation.International journal of molecular sciences · 2026Review
- Exploring the Lung-Liver Axis in Pulmonary Arterial Hypertension.Comprehensive Physiology · 2026Article
- Activin A-Endothelin-1 Axis Governs Pulmonary Vascular Remodeling: Mechanistic Basis for Emerging Therapies in PAH.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- Endothelial C-type natriuretic peptide/guanylyl cyclase-B signaling prevents pulmonary arterial hypertension.Nature communications · 2026Article
- Article
- The Role of the Apelin Receptor in the Pathophysiology of Pulmonary Arterial Hypertension.Cells · 2026Review
- The Pathophysiology, Mechanism, Diagnosis, and Management of Pulmonary Arterial Hypertension: A Comprehensive Literature Review.US cardiology · 2026Review
- Serum Activin A Level and 1-Year Mortality in Atrial Septal Defect-Associated Pulmonary Artery Hypertension: A Case-Control Study From the COHARD-PH Registry.International journal of vascular medicine · 2026Article
- Mannose and phenylboronate ester functionalized mesoporous silica nanoparticles contained in chitosan microneedles for enhancing cellular immunity and antitumor efficacy.Theranostics · 2026Article
- Cell biomechanics on muscle atrophy: from intricate mechanisms to therapeutic frontiers.Annals of medicine · 2025Review
- The activin pathway in chronic thromboembolic pulmonary hypertension: a potential biomarker for residual pulmonary hypertension after endarterectomy.ERJ open research · 2025Article
- Activin A-Activated ALK4 Induces Pathogenic Th17-Involved Endothelial-Mesenchymal Transition in Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Sotatercept in pulmonary arterial hypertension: revolution, risk and the road ahead.The European respiratory journal · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Activin-A Regulates Bone Morphogenetic Protein Signaling in Pulmonary Endothelial Cells Without Affecting Bone Morphogenetic Protein Type-II Receptor Expression.Pulmonary circulation · 2025Article
- From basic scientific research to the development of new drugs for pulmonary arterial hypertension: insights from activin-targeting agents.Breathe (Sheffield, England) · 2025Review
- Mechanisms of lung endothelial cell injury and survival in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary arterial hypertension is a progressive fatal disease that is characterized by pathological pulmonary artery remodeling, in which endothelial cell dysfunction is critically involved. We herein describe a previously unknown role of endothelial angiocrine in pulmonary hypertension. By searching for genes highly expressed in lung microvascular endothelial cells, we identify inhibin-β-A as an angiocrine factor produced by pulmonary capillaries. We find that excess production of inhibin-β-A by endothelial cells impairs the endothelial function in an autocrine manner by functioning as activin-A. Mechanistically, activin-A induces bone morphogenetic protein receptor type 2 internalization and targeting to lysosomes for degradation, resulting in the signal deficiency in endothelial cells. Of note, endothelial cells isolated from the lung of patients with idiopathic pulmonary arterial hypertension show higher inhibin-β-A expression and produce more activin-A compared to endothelial cells isolated from the lung of normal control subjects. When endothelial activin-A-bone morphogenetic protein receptor type 2 link is overdriven in mice, hypoxia-induced pulmonary hypertension was exacerbated, whereas conditional knockout of inhibin-β-A in endothelial cells prevents the progression of pulmonary hypertension. These data collectively indicate a critical role for the dysregulated endothelial activin-A-bone morphogenetic protein receptor type 2 link in the progression of pulmonary hypertension, and thus endothelial inhibin-β-A/activin-A might be a potential pharmacotherapeutic target for the treatment of pulmonary arterial hypertension.
Indexed as
Identifiers
What Socratic 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 Socratic graph.