Serum Hepcidin and Macrophage Iron Correlate With MCP-1 Release and Vascular Damage in Patients With Metabolic Syndrome Alterations
Autor: | Anna Ludovica Fracanzani, Luca Valenti, Paola Bonara, Dorine W. Swinkels, L. Burdick, Cecelia Frugoni, Silvia Fargion, Raffaela Rametta, Benedetta Maria Motta, Paola Dongiovanni |
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Rok vydání: | 2011 |
Předmět: |
Carotid Artery Diseases
Male medicine.medical_treatment Iron metabolism Pathogenesis and modulation of inflammation [IGMD 7] medicine.disease_cause Ferric Compounds Severity of Illness Index Mass Spectrometry risk factors Macrophage Ultrasonography Doppler Color Cells Cultured Chemokine CCL2 Metabolic Syndrome Middle Aged Cytokine Female Inflammation Mediators Cardiology and Cardiovascular Medicine free radicals/free-radical scavengers medicine.drug Adult medicine.medical_specialty Iron Enzyme-Linked Immunosorbent Assay Biology Hepcidins atherosclerosis cytokines iron macrophages Hepcidin Internal medicine medicine Humans RNA Messenger Hemochromatosis Aged Chi-Square Distribution Interleukin-6 Macrophages medicine.disease Iron Metabolism Disorders Quaternary Ammonium Compounds Oxidative Stress Endocrinology Ferritins Immunology biology.protein Ferric Metabolic syndrome Ex vivo Oxidative stress Antimicrobial Cationic Peptides |
Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology, 31, 683-90 Arteriosclerosis, Thrombosis, and Vascular Biology, 31, 3, pp. 683-90 |
ISSN: | 1524-4636 1079-5642 |
Popis: | Objective— Increased body iron stores and hepcidin have been hypothesized to promote atherosclerosis by inducing macrophage iron accumulation and release of cytokines, but direct demonstration in human cells is lacking. The aim of this study was to evaluate the effect of iron on cytokine release in monocytes ex vivo and the correlation with vascular damage and to evaluate the relationship among serum levels of hepcidin, cytokines, and vascular damage in patients with metabolic syndrome alterations. Methods and Results— Manipulation of iron status with ferric ammonium citrate and hepcidin-25 induced monocyte chemoattractant protein (MCP)-1 and interleukin-6 in human differentiating monocytes of patients with hyperferritinemia associated with the metabolic syndrome (n=11), but not in subjects with hemochromatosis or HFE mutations impairing iron accumulation (n=15), and the degree of induction correlated with the presence of carotid plaques, detected by echocolor–Doppler. In monocytes of healthy subjects (n=7), iron and hepcidin increased the mRNA levels and release of MCP-1, but not of interleukin-6. In 130 patients with metabolic alterations, MCP-1 levels, as detected by ELISA, were correlated with hepcidin-25 measured by time-of-flight mass spectrometry ( P =0.005) and were an independent predictor of the presence of carotid plaques ( P =0.05). Conclusion— Hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in high-risk individuals with metabolic alterations. |
Databáze: | OpenAIRE |
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