title: Potential contribution of the hepcidin-macrophage axis to plaque vulnerability in acute myocardial infarction in human.
abstract: OBJECTIVE
  Hepcidin-25 serves as a key peptide in the regulation of iron homeostasis and inflammation. It remains unknown whether hepcidin-25 plays an adverse role in atherosclerotic diseases. The aim of this study was to investigate whether hepcidin-25 is involved in the pathophysiology of coronary plaque vulnerability.
  
  
  RESULTS
  Serum hepcidin-25 levels were quantitatively determined by the LC-MS/MS assay system. Peripheral blood was collected from patients with acute myocardial infarction (MI, n=33) and patients with stable angina pectoris (sCAD, n=19). The levels of hepcidin-25, IL-6, and CRP were significantly higher in the patients with acute MI than in the patients with sCAD. Coronary blood was aspirated from the culprit arteries via a thrombectomy catheter in 16 of the MI patients. Serum from the aspirates contained higher levels of hepcidin-25 and IL-6 compared with the peripheral blood. In immunohistochemical staining, the macrophages of the plaques in the solid component of the aspirates were immunoreactive for hepcidin-25. To confirm the clinical observation, an in vitro study was performed using human macrophages and coronary endothelial cells. The hepcidin gene and protein were detected in the cultured macrophages but not in the endothelial cells. Hepcidin-25 exposure induced ferroportin degradation and reduced the survival rate of endothelial cells.
  
  
  CONCLUSIONS
  The results of the present study demonstrated that circulating hepcidin-25 and IL-6 were both elevated in the acute phase of MI and that hepcidin-25 released from plaque macrophages and other cell sources contributed to the plaque instability by inducing endothelial cell death.
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan; Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sasai
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan; Showa University Research Institute for Sport and Exercise Sciences, Yokohama, Japan. Electronic address: yiso@med.showa-u.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iso
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.affiliation: Showa University Research Institute for Sport and Exercise Sciences, Yokohama, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Sambe
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D064451:Hepcidins; C545475:hepcidin 25, human
keywords: Hepcidin-25; Interleukin-6; Macrophages; Myocardial infarction; Plaque vulnerability