Serum hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations

Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):683-90. doi: 10.1161/ATVBAHA.110.214858. Epub 2010 Dec 23.


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).

Conclusions: Hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in high-risk individuals with metabolic alterations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimicrobial Cationic Peptides / blood*
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / etiology*
  • Carotid Artery Diseases / immunology
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Chi-Square Distribution
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Ferric Compounds / pharmacology
  • Ferritins / blood
  • Hepcidins
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / metabolism
  • Iron / metabolism*
  • Iron Metabolism Disorders / blood
  • Iron Metabolism Disorders / complications*
  • Iron Metabolism Disorders / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Mass Spectrometry
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / immunology
  • Middle Aged
  • Oxidative Stress
  • Quaternary Ammonium Compounds / pharmacology
  • RNA, Messenger / metabolism
  • Severity of Illness Index
  • Ultrasonography, Doppler, Color


  • Antimicrobial Cationic Peptides
  • CCL2 protein, human
  • Chemokine CCL2
  • Ferric Compounds
  • HAMP protein, human
  • Hepcidins
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Quaternary Ammonium Compounds
  • RNA, Messenger
  • Ferritins
  • Iron
  • ferric ammonium citrate