ArticleArteriosclerosis, thrombosis, and vascular biology2012
Pharmacological suppression of hepcidin increases macrophage cholesterol efflux and reduces foam cell formation and atherosclerosis.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 142 citations in OpenAlex.
- Effects of serial phlebotomy on vascular endothelial function: Results of a prospective double-blind randomized study.Cardiovascular therapeutics · 2018Trial
- The statin-iron nexus: anti-inflammatory intervention for arterial disease prevention.American journal of public health · 2013Trial
- Red Blood Cell Distribution Width Is a Biomarker of Red Cell Dysfunction Associated with Inflammation, Macrophage Polarization, and Coronary Artery Calcification: A Prognostic Marker in Cardiovascular Disease and a Potential Target for Anti-Cytokine Therapy.Life (Basel, Switzerland) · 2026Review
- Insights Into Macrophage Ferroptosis: Implications for Atherosclerosis.Cell proliferation · 2026Review
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Essential and Non-Essential Metals and Metalloids and Their Role in Atherosclerosis.Cardiovascular toxicology · 2025Review
- The Role of Iron in Atherosclerosis and its Association with Related Diseases.Current atherosclerosis reports · 2024Review
- Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study.Cardiovascular diabetology · 2024Article
- Oxidative Stress-Mediated Programmed Cell Death: a Potential Therapy Target for Atherosclerosis.Cardiovascular drugs and therapy · 2024Review
- Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Ironing out macrophages in atherosclerosis.Acta biochimica et biophysica Sinica · 2023Review
- Review of the Protective Mechanism of Paeonol on Cardiovascular Disease.Drug design, development and therapy · 2023Review
- The role of iron metabolism in chronic diseases related to obesity.Molecular medicine (Cambridge, Mass.) · 2022Review
- Iron Metabolism Markers and Lower Extremity Arterial Disease in People with Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- A review on therapeutical potential of paeonol in atherosclerosis.Frontiers in pharmacology · 2022Review
- In-depth review: is hepcidin a marker for the heart and the kidney?Molecular and cellular biochemistry · 2021Review
- Non-Transferrin-Bound Iron in the Spotlight: Novel Mechanistic Insights into the Vasculotoxic and Atherosclerotic Effect of Iron.Antioxidants & redox signaling · 2021Review
- The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology.International journal of molecular sciences · 2021Review
- Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis.International journal of molecular sciences · 2021Review
- Intravenous iron therapy and the cardiovascular system: risks and benefits.Clinical kidney journal · 2021Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveWe recently reported that lowering of macrophage free intracellular iron increases expression of cholesterol efflux transporters ABCA1 and ABCG1 by reducing generation of reactive oxygen species. In this study, we explored whether reducing macrophage intracellular iron levels via pharmacological suppression of hepcidin can increase macrophage-specific expression of cholesterol efflux transporters and reduce atherosclerosis. METHODS AND
resultsTo suppress hepcidin, increase expression of the iron exporter ferroportin, and reduce macrophage intracellular iron, we used a small molecule inhibitor of bone morphogenetic protein (BMP) signaling, LDN 193189 (LDN). LDN (10 mg/kg IP b.i.d.) was administered to mice, and its effects on atherosclerosis, intracellular iron, oxidative stress, lipid efflux, and foam cell formation were measured in plaques and peritoneal macrophages. Long-term LDN administration to apolipoprotein E-/- mice increased ABCA1 immunoreactivity within intraplaque macrophages by 3.7-fold (n=8; P=0.03), reduced Oil Red O-positive lipid area by 50% (n=8; P=0.02), and decreased total plaque area by 43% (n=8; P=0.001). LDN suppressed liver hepcidin transcription and increased macrophage ferroportin, lowering intracellular iron and hydrogen peroxide production. LDN treatment increased macrophage ABCA1 and ABCG1 expression, significantly raised cholesterol efflux to ApoA-1, and decreased foam cell formation. All preceding LDN-induced effects on cholesterol efflux were reversed by exogenous hepcidin administration, suggesting modulation of intracellular iron levels within macrophages as the mechanism by which LDN triggers these effects.
conclusionsThese data suggest that pharmacological manipulation of iron homeostasis may be a promising target to increase macrophage reverse cholesterol transport and limit atherosclerosis.
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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.