Cited by 271Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionIron Metabolism and Disorders

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Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease

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Duffy, Stephen J., Biegelsen, Elizabeth S., Holbrook, Monika, Russell, Judson D., Gokce, Noyan, Keaney, John F., Vita, Joseph A.·2001·Circulation

DOI 10.1161/01.cir.103.23.2799

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Abstract

Background —Some epidemiological studies have shown that increased iron stores are associated with increased cardiovascular events. Redox-active iron may contribute to lipid peroxidation, endothelial cell activation, and generation of reactive oxygen species (especially hydroxyl radical, via Fenton chemistry). Increased oxidative stress is associated with impaired action of endothelium-derived nitric oxide in patients with atherosclerosis. Methods and Results —To test the hypothesis that reducing vascular iron stores would reverse endothelial dysfunction, we examined the effects of the iron chelator deferoxamine (500 mg intra-arterially over 1 hour) on vasomotor function in forearm resistance vessels of patients with coronary artery disease by venous occlusion plethysmography. Patients with coronary artery disease had impaired endothelium-dependent vasodilation in response to methacholine compared with healthy control subjects ( P <0.001). Deferoxamine infusion decreased serum iron levels ( P <0.001). Deferoxamine improved the blood flow response to methacholine in patients with coronary artery disease ( P <0.01 by 2-way repeated-measures ANOVA) but had no effect on the response to sodium nitroprusside. In normal volunteers, deferoxamine had no effect on the response to methacholine. The nitric oxide synthase inhibitor N G -monomethyl- l -arginine abolished augmentation of the methacholine response associated with deferoxamine. The hydroxyl radical scavenger mannitol had no effect on the methacholine response. Conclusions —Deferoxamine improved nitric oxide–mediated, endothelium-dependent vasodilation in patients with coronary artery disease. These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis.

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Authors: Duffy, S. J., Biegelsen, E. S., Holbrook, M., Russell, J. D., Gokce, N., Keaney, J. F., & Vita, J. A.
Affiliations: Boston University (US)
ORCID: Duffy, Stephen J.
Gokce, Noyan
Keaney, John F.
Vita, Joseph A.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2001-06-12
Volume: 103
Issue: 23
Pages: 2799-2804
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.103.23.2799
OpenAlex: W2006984835
Cited by: 271
References: 34
Citations by year: 2026: 4 · 2025: 6 · 2024: 10 · 2023: 10 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 11 · 2013: 11 · 2012: 12
FWCI: 12.78
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
National Institutes of Health (5r01hl052936-04, 5r01hl059346-02, 1r01hl053398-01a1)
Medical Research Council
National Health and Medical Research Council
National Medical Research Council
National Heart, Lung, and Blood Institute (K23 HL 04425, HL59346, HL 53398, HL 55993, P01HL055854, HL-100088, HL58976, R01HL058976, HL-55854, K23HL004425, P50HL055993, HL-52936)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords: iron chelation, deferoxamine, endothelial dysfunction, coronary artery disease, nitric oxide, endothelium-dependent vasodilation, oxidative stress, hydroxyl radicals, Fenton reaction, atherosclerosis, methacholine responsiveness, forearm resistance vessels, L-NMMA
MeSH terms: Adult, Blood Flow Velocity, Coronary Disease, Deferoxamine, Endothelium, Vascular, Enzyme Inhibitors, Female, Forearm, Humans, Infusions, Intra-Arterial, Iron, Iron Chelating Agents, Male, Middle Aged, Nitroprusside, Plethysmography, Vasodilation, Vasomotor System, Free Radical Scavengers, Methacholine Chloride, Nitric Oxide Synthase, omega-N-Methylarginine

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Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease

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