Abstract

The cardiovascular system requires iron to maintain its high energy demands and metabolic activity. Iron plays a critical role in oxygen transport and storage, mitochondrial function, and enzyme activity. However, excess iron is also cardiotoxic due to its ability to catalyze the formation of reactive oxygen species and promote oxidative damage. While mammalian cells have several redundant iron import mechanisms, they are equipped with a single iron-exporting protein, which makes the cardiovascular system particularly sensitive to iron overload. As a result, iron levels are tightly regulated at many levels to maintain homeostasis. Iron dysregulation ranges from iron deficiency to iron overload and is seen in many types of cardiovascular disease, including heart failure, myocardial infarction, anthracycline-induced cardiotoxicity, and Friedreich's ataxia. Recently, the use of intravenous iron therapy has been advocated in patients with heart failure and certain criteria for iron deficiency. Here, we provide an overview of systemic and cellular iron homeostasis in the context of cardiovascular physiology, iron deficiency, and iron overload in cardiovascular disease, current therapeutic strategies, and future perspectives.

MeSH

Heart Failure, Cardiovascular System, Physiology, Homeostasis, Macrophages, Cardiovascular Diseases, Therapeutics, Iron Overload

Cited by

• Iron Deficiency Treatment in Heart Failure-Challenges and Therapeutic Solutions. J Clin Med, 2025
• The role of impaired iron transport on exercise performance and prognosis in patients with chronic heart failure. Int J Cardiol Heart Vasc, 2025
• Intravenous Ferric Carboxymaltose in Heart Failure With Iron Deficiency: The FAIR-HF2 DZHK05 Randomized Clinical Trial. JAMA, 2025
• Endothelial transferrin receptor 1 contributes to thrombogenesis through cascade ferroptosis. Redox Biol, 2024
• Anthracycline Cardiotoxicity in Adult Cancer Patients: State-of-the-Art Review. JACC CardioOncol, 2024
• Genetic Susceptibility to Causal Relationship Between Iron Metabolism Disorder Involving Immunocytes and Risk of Pneumonia and Sepsis. Food Sci Nutr, 2025
• The mechanism of ferroptosis and its related diseases. Mol Biomed, 2023
• The Interplay Between Carotid Intima-Media Thickness and Selected Serum Biomarkers in Various Stages of Chronic Kidney Disease. Biomedicines, 2025
• A Cardiac-Targeting and Anchoring Bimetallic Cluster Nanozyme Alleviates Chemotherapy-Induced Cardiac Ferroptosis and PANoptosis. Adv Sci (Weinh), 2025
• Evolution of Theories on Doxorubicin-Induced Late Cardiotoxicity-Role of Topoisomerase. Int J Mol Sci, 2025
• Pyridoxamine Limits Cardiac Dysfunction in a Rat Model of Doxorubicin-Induced Cardiotoxicity. Antioxidants (Basel), 2024
• Iron chelating, antioxidant and anti-apoptotic activities of hesperidin and/or rutin against induced-ferroptosis in heart tissue of rats. Int J Immunopathol Pharmacol, 2025
• Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia. Int J Biol Sci, 2024
• Associations Between Hemoglobin and Serum Iron Levels and the Risk of Mortality Among Patients with Coronary Artery Disease. Nutrients, 2025
• Recent research progress on metal ions and metal-based nanomaterials in tumor therapy. Front Bioeng Biotechnol, 2025
• Ferroptosis induced by environmental pollutants and its health implications. Cell Death Discov, 2025
• Mechanistic Investigation of Salidroside Modulates Iron Overload to Mitigate Radiation-Induced Heart Disease. Cardiovasc Ther, 2026
• Perilipin 5 alleviates ferroptosis of cardiomyocytes by targeting USP10-p53-TfR proteasome-dependent degradation. Front Med (Lausanne), 2025
• Biological function of RNA-binding proteins in myocardial infarction: a potential emerging therapeutic limelight. Cell Biosci, 2025
• Novel biallelic variants in IREB2 cause an early-onset neurodegenerative disorder in a Chinese pedigree. Orphanet J Rare Dis, 2024