New insights into the role of iron in inflammation and atherosclerosis

Iron is fundamental for life-essential processes. However, it can also cause oxidative damage, which is thought to trigger numerous pathologies, including cardiovascular diseases. The role of iron in the pathogenesis of atherosclerosis is still not completely understood. Macrophages are both key players in the handling of iron throughout the body and in the onset, progression and destabilization of atherosclerotic plaques. Iron itself might impact atherosclerosis through its effects on macrophages. However, while targeting iron metabolism within macrophages may have some beneficial effects on preventing atherosclerotic plaque progression there may also be negative consequences. Thus, the prevailing view of iron being capable of accelerating the progression of coronary disease through lipid peroxidation may not fully take into account the multi-faceted role of iron in pathogenesis of atherosclerosis. In this review, we will summarize the current understanding of iron metabolism in the context of the complex interplay between iron, inflammation, and atherosclerosis.

• Publication year

  2019

• Venue

  EBioMedicine

• Publication date

  2019-08-12

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.ebiom.2019.08.014PMID 31416722PMCID 6796517
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank

  2019cited by this paper
• Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction.

  2019cited by this paper
• Iron alters macrophage polarization status and leads to steatohepatitis and fibrogenesis

  2019cited by this paper
• Hepcidin Deficiency Protects Against Atherosclerosis

  2019cited by this paper
• Iron Deficiency in Heart Failure: An Overview.

  2019cited by this paper
• Lysed Erythrocyte Membranes Promote Vascular Calcification: Possible Role of Erythrocyte-Derived Nitric Oxide

  2019cited by this paper
• A Smart pH-Sensitive Delivery System for Enhanced Anticancer Efficacy via Paclitaxel Endosomal Escape

  2019cited by this paper
• Effects of Genetically Determined Iron Status on Risk of Venous Thromboembolism and Carotid Atherosclerotic Disease: A Mendelian Randomization Study

  2019cited by this paper
• Macrophage Death as a Pharmacological Target in Atherosclerosis

  2019cited by this paper
• CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis

  2018cited by this paper
• Long-term donors versus non-donor men: Iron metabolism and the atherosclerotic process.

  2018cited by this paper
• Effects of serial phlebotomy on vascular endothelial function: Results of a prospective double‐blind randomized study

  2018cited by this paper
• Potential health hazards of eating red meat

  2017cited by this paper
• Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease.

  2017cited by this paper
• Associations of plasma hepcidin with mortality risk in patients with coronary artery disease

  2017cited by this paper
• A Red Carpet for Iron Metabolism.

  2017cited by this paper
• Linking Hemorrhage, Angiogenesis, Macrophages, and Iron Metabolism in Atherosclerotic Vascular Diseases

  2017cited by this paper
• The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study—Brief Report

  2017cited by this paper
• Association Between Carotid Atherosclerotic Plaque Calcification and Intraplaque Hemorrhage: A Magnetic Resonance Imaging Study

  2017cited by this paper
• Mendelian Randomization.

  2017cited by this paper
• Correlates of serum hepcidin levels and its association with cardiovascular disease in an elderly general population

  2016cited by this paper
• Novel Ferroptosis Inhibitors with Improved Potency and ADME Properties.

  2016cited by this paper
• Iron and hepcidin as risk factors in atherosclerosis: what do the genes say?

  2015cited by this paper
• A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

  2015cited by this paper
• Regulation of ferroptotic cancer cell death by GPX4.

  2014cited by this paper
• Serum Hepcidin Is Associated With Presence of Plaque in Postmenopausal Women of a General Population

  2014cited by this paper
• Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

  2014cited by this paper
• Role of Proinflammatory CD68+ Mannose Receptor− Macrophages in Peroxiredoxin-1 Expression and in Abdominal Aortic Aneurysms in Humans

  2013cited by this paper
• Iron: Protector or Risk Factor for Cardiovascular Disease? Still Controversial

  2013cited by this paper
• Pathophysiology of atherosclerosis plaque progression.

  2013cited by this paper
• Pharmacologic Suppression of Hepcidin Increases Macrophage Cholesterol Efflux and Reduces Foam Cell Formation and Atherosclerosis

  2012cited by this paper
• Large-scale association analysis identifies new risk loci for coronary artery disease

  2012cited by this paper
• Activating Transcription Factor 1 Directs Mhem Atheroprotective Macrophages Through Coordinated Iron Handling and Foam Cell Protection

  2012cited by this paper
• Ferroptosis: an iron-dependent form of nonapoptotic cell death.

  2012cited by this paper
• Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses.

  2011cited by this paper
• Monocyte and macrophage dynamics during atherogenesis.

  2011cited by this paper
• Iron stores are associated with asymptomatic atherosclerosis in healthy men of primary prevention

  2011cited by this paper
• Getting folic acid nutrition right.

  2010cited by this paper
• Iron bioavailability and dietary reference values.

  2010cited by this paper
• Hemochromatosis (HFE) genotype and atherosclerosis: Increased susceptibility to iron-induced vascular damage in C282Y carriers?

  2010cited by this paper
• Regulation of hepcidin and iron-overload disease.

  2009cited by this paper
• Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice.

  2009cited by this paper
• Do Hemochromatosis Mutations Protect Against Iron-Mediated Atherogenesis?

  2009cited by this paper
• Oxidized Hemoglobin Is an Endogenous Proinflammatory Agonist That Targets Vascular Endothelial Cells*

  2009cited by this paper
• Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype.

  2009influential reference
• Autocrine formation of hepcidin induces iron retention in human monocytes.

  2008cited by this paper
• Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice.

  2008cited by this paper
• Mutations in the HFE Gene and Cardiovascular Disease Risk: An Individual Patient Data Meta-Analysis of 53 880 Subjects

  2008cited by this paper
• Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism.

  2008cited by this paper
• Attenuated Inflammatory Responses in Hemochromatosis Reveal a Role for Iron in the Regulation of Macrophage Cytokine Translation1

  2008cited by this paper
• PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties.

  2007cited by this paper
• Iron imports. IV. Hepcidin and regulation of body iron metabolism.

  2006cited by this paper
• TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens.

  2006cited by this paper
• Iron Stores and Vascular Function in Voluntary Blood Donors

  2005cited by this paper
• [Mendelian randomization].

  2005cited by this paper
• The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.

  2005influential reference
• Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization

  2004cited by this paper
• Association Between High Serum Ferritin Levels and Carotid Atherosclerosis in the Study of Health in Pomerania (SHIP)

  2004cited by this paper
• Role of Toll‐like receptor 4 in the initiation and progression of atherosclerotic disease

  2004cited by this paper
• Intraplaque hemorrhage and progression of coronary atheroma.

  2003cited by this paper
• Alternative activation of macrophages

  2003cited by this paper
• Iron activates NF-kappaB in Kupffer cells.

  2002cited by this paper
• Iron activates NF-κB in Kupffer cells

  2002cited by this paper
• Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells.

  2002cited by this paper
• Oxidized Low Density Lipoprotein (ox-LDL) Binding to ox-LDL Receptor-1 in Endothelial Cells Induces the Activation of NF-κB through an Increased Production of Intracellular Reactive Oxygen Species*

  2000cited by this paper
• Haemochromatosis: Automated Detection of the Two Point Mutations in the HFE Gene: Cys282Tyr and His63Asp

  2000cited by this paper
• Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation : a prospective cohort study in men in eastern Finland.

  1999cited by this paper
• Iron loading and disease surveillance.

  1999cited by this paper
• Coronary heart disease and iron status: meta-analyses of prospective studies.

  1999influential reference
• Association between body iron stores and the risk of acute myocardial infarction in men.

  1998cited by this paper
• Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro.

  1995cited by this paper
• No association between serum ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study.

  1995cited by this paper
• Hemochromatosis, multiorgan hemosiderosis, and coronary artery disease.

  1994cited by this paper
• Body iron stores and presence of carotid atherosclerosis. Results from the Bruneck Study.

  1994cited by this paper
• Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions.

  1992cited by this paper
• High Stored Iron Levels Are Associated With Excess Risk of Myocardial Infarction in Eastern Finnish Men

  1992cited by this paper
• Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury.

  1991cited by this paper
• Iron and the sex difference in heart disease risk.

  1981cited by this paper

• A review on computational assessment of biomedical markers in carotid arteries

  2026cites this paper
• Role of Iron Metabolism in Obesity, Type 2 Diabetes Mellitus, Atherosclerotic Cardiovascular Disease, and Metabolic Dysfunction-Associated Steatotic Liver Disease – A Narrative Review

  2026cites this paper
• Evaluation of the protective effects of selenium against iron overload-induced toxicity in rats using a multiple-markers approach.

  2026cites this paper
• Key role of the CSE/transsulfuration pathway in macrophage phenotypic change under iron overload.

  2025cites this paper
• Ferroptosis, pathogenesis and therapy in AS co-depression disease

  2025cites this paper
• Perfluorooctane sulfonate induced ferritinophagy via detyrosinated alpha tubulin-TRIM21-HERC2-regulated NCOA4 degradation in hepatocytes.

  2025cites this paper
• Impact of inflammatory status on intestinal iron absorption in older hospitalized patients

  2025cites this paper
• Lactoferrin—A Regulator of Iron Homeostasis and Its Implications in Cancer

  2025cites this paper
• Essential and Non-Essential Metals and Metalloids and Their Role in Atherosclerosis

  2025cites this paper
• Iron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism

  2025cites this paper
• Natural products and ferroptosis: A novel approach for heart failure management.

  2025cites this paper
• Serum ferritin and risk of stroke: a meta-analysis of observation studies

  2025cites this paper
• Impact of Sappan Wood Extract as Iron Chelator Adjuvant on Iron Concentration and Macrophage Polarization in Rat Spleen

  2025cites this paper
• Clinical Outcomes of Iron Supplement Therapy in Non-Anemic Female CKD Stage 3 Patients with Low Serum Ferritin Level: A Multi-Institutional TriNetX Analysis

  2025cites this paper
• Association Between Hemoglobin‐to‐Red Blood Cell Distribution Width Ratio and Arterial Stiffness

  2025cites this paper
• Multidimensional analysis of cerebral iron and vascular changes in chronic unilateral middle cerebral artery stenosis with quantitative susceptibility mapping, arterial spin labeling and high-resolution vessel wall imaging—a pilot study

  2025cites this paper
• Baseline CSF ferritin levels were associated with trajectories of depressive symptoms among older people without dementia

  2025cites this paper
• NDRG1 as a sensor and mediator of endothelial stress: from homeostasis to inflammation and cardiovascular disease

  2025cites this paper
• Insights Into Macrophage Ferroptosis: Implications for Atherosclerosis

  2025cites this paper
• U-shaped association between hemoglobin to red blood cell distribution width ratio and all-cause mortality among critically ill pediatric patients

  2025cites this paper
• In Situ Conversion of Atherosclerotic Plaques' Iron into Nanotheranostics.

  2025cites this paper
• Phase-dependent iron depletion differentially regulates the niche of intestinal stem cells in experimental colitis via ERK/STAT3 signaling pathway

  2025cites this paper
• The Association of Dietary Micronutrient Intake and Systemic Inflammation among Patients with Type 2 Diabetes: A Cross-Sectional Study

  2024cites this paper
• Ferroptosis in eye diseases: a systematic review

  2024cites this paper
• Analysis of mechanism, therapeutic strategies, and potential natural compounds against atherosclerosis by targeting iron overload-induced oxidative stress.

  2024cites this paper
• Iron citrate Synthesit: impact on blood parameters in non-iron deficient models

  2024cites this paper
• Regression-derived optimal milk thistle in growing quail's diet

  2024cites this paper
• Dietary iron intake aggravates dyslipidaemia by elevating ferritin levels in patients with insulin resistance and cardiovascular diseases: A cross-sectional study

  2024cites this paper
• Phenolics and terpenoids with good anti-inflammatory activity from the fruits of Amomum villosum and the anti-inflammatory mechanism of active diterpene.

  2024cites this paper
• Inverted U‐Shaped Association of Plasma Resolvin D2 With Atherosclerotic Cardiovascular Disease and the Mediation Effects of Serum Cholesterol: A Chinese Community‐Based Study

  2024cites this paper
• Pharmacological models of liver iron overload

  2024cites this paper
• Salubrinal promotes phospho-eIF2α-dependent activation of UPR leading to autophagy-mediated attenuation of iron-induced insulin resistance

  2024cites this paper
• GPX4 overexpression does not alter atherosclerotic plaque development in ApoE knock-out mice

  2024cites this paper
• Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases.

  2024cites this paper
• Zinc finger translocation‑associated protein promotes ferroptosis through the upregulation of ACSL4 expression in vascular endothelial cells

  2024cites this paper
• Iron Deficiency in Pulmonary Hypertension.

  2024cites this paper
• Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

  2024cites this paper
• The Protective Role of Interleukin-37 in Cardiovascular Diseases through Ferroptosis Modulation

  2024cites this paper
• Silencing ARL11 relieved atherosclerotic inflammation and lipid deposition via retraining JAK2/STAT1 pathway.

  2024cites this paper
• The complex interplay between ferroptosis and atherosclerosis.

  2024cites this paper
• Iron, lipid peroxidation and ferroptosis play pathogenic roles in atherosclerosis.

  2024cites this paper
• Iron Deficiency Promotes Intra-leaflet Haemorrhage-induced Aortic Valve Calcification: an Experimental Study.

  2024cites this paper
• Intravenous iron treatment fuels chronic kidney disease‐induced arterial media calcification in rats

  2024cites this paper
• Hemoglobin-to-red blood cell distribution width ratio is negatively associated with stroke: a cross-sectional study from NHANES

  2024cites this paper
• The Role of Iron in Atherosclerosis and its Association with Related Diseases

  2024cites this paper
• Retrospective analysis of ferrotherapy methodology in patients with chronic heart failure and chronic kidney disease

  2024cites this paper
• Iron Overload and Abdominal Aortic Aneurysm

  2024cites this paper
• Improving understanding of ferroptosis: Molecular mechanisms, connection with cellular senescence and implications for aging

  2024cites this paper
• The polymorphic locus rs1799945 of the HFE gene determines the risk of severe preeclampsia

  2023cites this paper
• The usefulness of initial serum ferritin level as a predictor of in-hospital mortality in STEMI.

  2023cites this paper
• Association between hemoglobin-to-red blood cell distribution width ratio and hospital mortality in patients with non-traumatic subarachnoid hemorrhage

  2023cites this paper
• Pioglitazone treatment increases the cellular acid-labile and protein-bound sulfane sulfur fractions.

  2023cites this paper
• Iron metabolism and atherosclerosis.

  2023cites this paper
• The Interplay between Intracellular Iron Homeostasis and Neuroinflammation in Neurodegenerative Diseases

  2023cites this paper
• Antioxidant and Lipid-Lowering Effects of Buriti Oil (Mauritia flexuosa L.) Administered to Iron-Overloaded Rats

  2023influential citation
• Predictive value of serum iron on heart failure in patients with acute ST‐segment elevation myocardial infarction

  2023cites this paper
• A Portable Measurement Device Based on Phenanthroline Complex for Iron Determination in Water

  2023cites this paper
• Vascular calcification: Molecular mechanisms and therapeutic interventions

  2023cites this paper
• Diagnostic value and method of soluble transferrin receptor for suspected coronary artery disease: a case-control study

  2023cites this paper
• Breast arterial calcification and the iron deficiency anemia in the young woman: is there a relationship?

  2023cites this paper
• Trace Elements Open a New Direction for the Diagnosis of Atherosclerosis

  2023cites this paper
• Multifunctional Carbon Quantum Dots: Iron Clearance and Antioxidation for Neuroprotection in Intracerebral Hemorrhage Mice.

  2023cites this paper
• Clinical utility of circulating TWEAK and CD163 as biomarkers of iron-induced cardiac decompensation in transfusion dependent thalassemia major.

  2023cites this paper
• Anticancer Effects of 6-Gingerol through Downregulating Iron Transport and PD-L1 Expression in Non-Small Cell Lung Cancer Cells

  2023cites this paper
• The relationship between asymptomatic atherosclerosis and hepcidin-25 in chronic kidney disease patients

  2023cites this paper
• The effect of circulating iron on barrier integrity of primary human endothelial cells

  2023cites this paper
• Accelerated Atherosclerosis in Beta Thalassemia.

  2023cites this paper
• Regulation of epidermal ferritin expression influences systemic iron homeostasis.

  2023cites this paper
• Fundamental Pathobiology of Coronary Atherosclerosis and Clinical Implications for Chronic Ischemic Heart Disease Management-The Plaque Hypothesis: A Narrative Review.

  2022cites this paper
• Decreased Iron Ion Concentrations in the Peripheral Blood Correlate with Coronary Atherosclerosis

  2022cites this paper
• Cardiovascular disease

  2022cites this paper
• Histopathological correlation of near infrared autofluorescence in human cadaver coronary arteries.

  2022cites this paper
• Role of Pyroptosis and Ferroptosis in the Progression of Atherosclerotic Plaques

  2022cites this paper
• The Prognostic Performance of Ferritin in Patients with Acute Myocardial Infarction: A Systematic Review

  2022cites this paper
• The Toxic Influence of Excess Free Iron on Red Blood Cells in the Biophysical Experiment: An In Vitro Study

  2022cites this paper
• NOD1 splenic activation confers ferroptosis protection and reduces macrophage recruitment under pro-atherogenic conditions.

  2022cites this paper
• Current advances in the imaging of atherosclerotic vulnerable plaque using nanoparticles

  2022cites this paper
• Secreted frizzled-related protein 4 exerts anti-atherosclerotic effects by reducing inflammation and oxidative stress.

  2022cites this paper
• Iron Withdrawal with DIBI, a Novel 3-Hydroxypyridin-4-One Chelator Iron-Binding Polymer, Attenuates Macrophage Inflammatory Responses

  2022cites this paper
• The Role of Iron in Atherosclerosis in Apolipoprotein E Deficient Mice

  2022cites this paper
• Role of Iron in Aging Related Diseases

  2022cites this paper
• Essential Trace Element Status in Systemic Lupus Erythematosus: a Meta-analysis Based on Case-Control Studies

  2022cites this paper
• Emerging Roles of the Iron Chelators in Inflammation

  2022influential citation
• Unraveling the interplay between iron homeostasis, ferroptosis and extramedullary hematopoiesis.

  2022cites this paper
• Lipid oxidation in pathophysiology of atherosclerosis: Current understanding and therapeutic strategies

  2022cites this paper
• Understanding the role of alternative macrophage phenotypes in human atherosclerosis

  2022influential citation
• Melatonin: Potential avenue for treating iron overload disorders

  2022cites this paper
• Predictive value of hemoglobin-to-red blood cell distribution width ratio for contrast-induced nephropathy after emergency percutaneous coronary intervention

  2022cites this paper
• New Progress in Early Diagnosis of Atherosclerosis

  2022cites this paper
• Potential intervention target of atherosclerosis: Ferroptosis

  2022cites this paper
• Reliability and Value of 3D Sequential QUantitative T1‐T2‐T2* MAppings (SQUMA) MR Multi‐Parametric Imaging in Characterizing Carotid Artery Atherosclerosis

  2022cites this paper
• Melittin regulates iron homeostasis and mediates macrophage polarization in rats with lumbar spinal stenosis.

  2022cites this paper
• RNA-Seq analysis of obese Pdha1fl/flLyz2-Cre mice induced by a high-fat diet

  2022cites this paper
• Neuroprotective Panel of Olive Polyphenols: Mechanisms of Action, Anti-Demyelination, and Anti-Stroke Properties

  2022cites this paper
• Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer’s Disease Progression

  2022cites this paper
• Outlook of Ferroptosis-Targeted Lipid Peroxidation in Cardiovascular Disease.

  2022cites this paper
• The Impacts of Iron Overload and Ferroptosis on Intestinal Mucosal Homeostasis and Inflammation

  2022cites this paper
• The Role of Macrophage Iron Overload and Ferroptosis in Atherosclerosis

  2022cites this paper
• High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue

  2022cites this paper
• Improving nutrition through biofortification–A systematic review

  2022cites this paper