ArticleProceedings of the National Academy of Sciences of the United States of America2019
Intracellular iron deficiency in pulmonary arterial smooth muscle cells induces pulmonary arterial hypertension in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Systematic review and meta-analysis of prolactin and iron deficiency in peripartum cardiomyopathy.Open heart · 2020Pooled it
- Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials.Annals of the American Thoracic Society · 2021Trial
- Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial.BMJ open respiratory research · 2020Trial
- Iron and the lung: emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
- Iron Deficiency in Pulmonary Hypertension-Prevalence, Impact on Prognosis and Disease Burden in Pulmonary Arterial Hypertension and Pulmonary Hypertension Related to Hypoxia: A Review.International journal of molecular sciences · 2026Review
- Reduced gastrointestinal iron uptake in pulmonary arterial hypertension: a prospective cross-sectional study.Respiratory research · 2026Article
- Article
- Interaction of ferroptosis and cuproptosis in the perspective of pulmonary hypertension.Frontiers in cardiovascular medicine · 2025Review
- The role of redox-active iron, copper, manganese, and redox-inactive zinc in toxicity, oxidative stress, and human diseases.EXCLI journal · 2025Review
- Control of Systemic Iron Homeostasis: Insights Gained from Studying Mouse Models.Advances in experimental medicine and biology · 2025Review
- Genome-Wide Approach of Gene-Nutrient Intake Interaction Study for Essential Hypertension in a Large Korean Cohort (KoGES).Nutrients · 2024Article
- Oxygen-sensing pathways and the pulmonary circulation.The Journal of physiology · 2024Review
- Regulated vascular smooth muscle cell death in vascular diseases.Cell proliferation · 2024Review
- The Role of Early Child Nutrition in Pulmonary Hypertension-A Narrative Review.Children (Basel, Switzerland) · 2024Review
- The hepcidin-ferroportin axis influences mitochondrial function, proliferation, and migration in pulmonary artery endothelial and smooth muscle cells.Pulmonary circulation · 2024Article
- Immature reticulocyte fraction: A novel biomarker of hemodynamic severity in pulmonary arterial hypertension.Pulmonary circulation · 2024Article
- Iron deficiency and supplementation in heart failure.Nature reviews. Cardiology · 2024Review
- Hypoxic pulmonary vasoconstriction does not limit maximal exercise capacity in healthy volunteers breathing 12% oxygen at sea level.Physiological reports · 2024Article
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Iron deficiency augments hypoxic pulmonary arterial pressure in healthy individuals and exacerbates pulmonary arterial hypertension (PAH) in patients, even without anemia. Conversely, iron supplementation has been shown to be beneficial in both settings. The mechanisms underlying the effects of iron availability are not known, due to lack of understanding of how cells of the pulmonary vasculature respond to changes in iron levels. The iron export protein ferroportin (FPN) and its antagonist peptide hepcidin control systemic iron levels by regulating release from the gut and spleen, the sites of absorption and recycling, respectively. We found FPN to be present in pulmonary arterial smooth muscle cells (PASMCs) and regulated by hepcidin cell autonomously. To interrogate the importance of this regulation, we generated mice with smooth muscle-specific knock in of the hepcidin-resistant isoform fpn C326Y. While retaining normal systemic iron levels, this model developed PAH and right heart failure as a consequence of intracellular iron deficiency and increased expression of the vasoconstrictor endothelin-1 (ET-1) within PASMCs. PAH was prevented and reversed by i.v. iron and by the ET receptor antagonist BQ-123. The regulation of ET-1 by iron was also demonstrated in healthy humans exposed to hypoxia and in PASMCs from PAH patients with mutations in bone morphogenetic protein receptor type II. Such mutations were further associated with dysregulation of the HAMP/FPN axis in PASMCs. This study presents evidence that intracellular iron deficiency specifically within PASMCs alters pulmonary vascular function. It offers a mechanistic underpinning for the known effects of iron availability in humans.
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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.