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
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