ArticleProceedings of the National Academy of Sciences of the United States of America2016
HIF2α-arginase axis is essential for the development of pulmonary hypertension.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 181 citations in OpenAlex.
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- Contemporary Endothelial Genome Editing Technologies: Towards Precision Genetic Medicine for Vascular Diseases.International journal of molecular sciences · 2026Review
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- Altitude hypoxia and hypoxemia: pathogenesis and management.Signal transduction and targeted therapy · 2026Review
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- Toward precision medicine in COPD: phenotypes, endotypes, biomarkers, and treatable traits.Respiratory research · 2025Review
- c-Myc promotes metabolic reprogramming in pulmonary hypertension via the stimulation of glutaminolysis and the reductive tricarboxylic acid cycle.Redox biology · 2025Article
- Will Stub1 Be the Next Target for Pulmonary Hypertension Therapy Development?American journal of respiratory cell and molecular biology · 2025Article
- Genetic adaptations shaping survival, pregnancy, and life at high altitude and sea level.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- The Interplay Between Pulmonary Hypertension and Atrial Fibrillation: A Comprehensive Overview.Cells · 2025Review
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- Iron Replacement Attenuates Hypoxic Pulmonary Hypertension by Remodeling Energy Metabolism via Regulating the HIF2α/Mitochondrial Complex I, III/ROS Axis.Biomolecules · 2025Article
- ARF6 as a Novel Activator of HIF-2α in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- Changes in Macrophages in Pulmonary Hypertension: A Focus on High-altitude Pulmonary Hypertension.Anatolian journal of cardiology · 2025Review
- Bioactive compound combinations fromFrontiers in pharmacology · 2025Article
- Exploring the interplay between mitochondria and endoplasmic reticulum in pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2025Review
- Oxygen-sensing pathways and the pulmonary circulation.The Journal of physiology · 2024Review
- Endothelial PHD2 deficiency induces apoptosis resistance and inflammation via AKT activation and AIP1 loss independent of HIF2α.American journal of physiology. Lung cellular and molecular physiology · 2024Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Hypoxic pulmonary vasoconstriction is correlated with pulmonary vascular remodeling. The hypoxia-inducible transcription factors (HIFs) HIF-1α and HIF-2α are known to contribute to the process of hypoxic pulmonary vascular remodeling; however, the specific role of pulmonary endothelial HIF expression in this process, and in the physiological process of vasoconstriction in response to hypoxia, remains unclear. Here we show that pulmonary endothelial HIF-2α is a critical regulator of hypoxia-induced pulmonary arterial hypertension. The rise in right ventricular systolic pressure (RVSP) normally observed following chronic hypoxic exposure was absent in mice with pulmonary endothelial HIF-2α deletion. The RVSP of mice lacking HIF-2α in pulmonary endothelium after exposure to hypoxia was not significantly different from normoxic WT mice and much lower than the RVSP values seen in WT littermate controls and mice with pulmonary endothelial deletion of HIF-1α exposed to hypoxia. Endothelial HIF-2α deletion also protected mice from hypoxia remodeling. Pulmonary endothelial deletion of arginase-1, a downstream target of HIF-2α, likewise attenuated many of the pathophysiological symptoms associated with hypoxic pulmonary hypertension. We propose a mechanism whereby chronic hypoxia enhances HIF-2α stability, which causes increased arginase expression and dysregulates normal vascular NO homeostasis. These data offer new insight into the role of pulmonary endothelial HIF-2α in regulating the pulmonary vascular response to hypoxia.
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