title: Serum hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  Hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in high-risk individuals with metabolic alterations.
authors.affiliation: Centro Malattie Metaboliche del Fegato, Department of Internal Medicine, Università degli Studi, Ospedale Maggiore Policlinico Ca' Granda IRCCS, Milano, Via F Sforza 35, 20122 Milano, Italy. luca.valenti@unimi.it
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.forename: Paola
authors.initials: P
authors.lastname: Dongiovanni
authors.forename: Benedetta Maria
authors.initials: BM
authors.lastname: Motta
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.forename: Paola
authors.initials: P
authors.lastname: Bonara
authors.forename: Raffaela
authors.initials: R
authors.lastname: Rametta
authors.forename: Larry
authors.initials: L
authors.lastname: Burdick
authors.forename: Cecelia
authors.initials: C
authors.lastname: Frugoni
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
mesh_terms: D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D005293:Ferritins / Q000097:blood; D064451:Hepcidins; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000097:blood / Q000150:complications* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000276:immunology; D008875:Middle Aged; D018384:Oxidative Stress; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D018615:Ultrasonography, Doppler, Color
chemical_list: D023181:Antimicrobial Cationic Peptides; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005290:Ferric Compounds; C578702:HAMP protein, human; D064451:Hepcidins; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D005293:Ferritins; D007501:Iron; C013531:ferric ammonium citrate