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

Luca Valenti, Paola Dongiovanni, Benedetta Maria Motta, Dorine W. Swinkels, Paola Bonara, Raffaela Rametta, Larry Burdick, Cecelia Frugoni, Anna Ludovica Fracanzani, Silvia Fargion

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish
Pages (from-to)683-690
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • atherosclerosis
  • cytokines
  • free radicals/free-radical scavengers
  • iron
  • macrophages
  • risk factors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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