Tohoku J. Exp. Med., 2009, 218(2)

Serum Hepcidin-20 is Elevated during the Acute Phase of Myocardial Infarction

HIROSHI SUZUKI,¹ KEN TOBA,² KIMINORI KATO,² TAKUYA OZAWA,² NAOHISA TOMOSUGI,³ MASATO HIGUCHI,³ TARO KUSUYAMA,¹ YOSHITAKA ISO,¹ NAOHIKO KOBAYASHI,⁴ SIN-ICHIRO YOKOYAMA,⁵ NOBORU FUKUDA,⁵ HIDEKI SAITOH,⁶ KOHEI AKAZAWA⁷ and YOSHIFUSA AIZAWA²

¹Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
²First Department of Internal Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
³Proteomics Research Unit, Kanazawa Medical University, Kanazawa, Japan
⁴Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Japan
⁵Department of Advanced Medicine, Nihon University School of Medicine, Tokyo, Japan
⁶Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
⁷Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata, Japan

Hepcidin, a key iron-regulator secreted from the liver, consists of 25 amino acids (hepcidin-25), blocks iron release from macrophages via internalization and degradation of cellular iron exporter ferroportin, and restrains the use of iron in organs. Hepcidin mRNA and protein are also expressed in the human heart. A short form of hepcidin that lacks 5 amino-acid residues in the N-terminus (hepcidin-20) has been found in human serum, although its physiological role is unknown. Here, we successfully measured the serum levels of hepcidin-25 and hepcidin-20 in 12 patients with acute myocardial infarction (AMI) using surface-enhanced laser desorption ionization time of flight mass spectrometry. Among the selected 10 patients, whose blood samples were taken within 4 hours after a heart attack, all the patients showed elevated serum levels of hepcidin-20 [between 31.7 and 285.1 arbitrary unit (AU); normal level < 9.3 AU], while 8 patients showed high levels of hepcidin-25 (9.3-271.4; normal < 25.5 AU). The hepcidin-20 level was decreased to nearly the normal level on day 7 (range of 2.9 to 12.5 AU) in the 12 patients, whereas the hepcidin-25 level remained high on day 7 in 8 patients. Furthermore, the elevated levels of hepcidin-25 and hepcidin-20 were not correlated with the serum levels of markers for inflammation, interleukin-6 and C-reactive protein, in the patients with AMI. In conclusion, the serum hepcidin-20 is transiently elevated in response to acute cardiac ischemia. Measurement of serum hepcidin-20, rather than hepcidin-25, is helpful for diagnosis of acute myocardial infarction.

Keywords —— Hepcidin; hepcidin-20; iron metabolism; myocardial infarction; proteomics.

© 2009 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2009, 218, 93-98

Correspondence: Ken Toba, First Department of Internal Medicine, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-Dori, Niigata 951-8510, Japan.

e-mail: tobaken@med.niigata-u.ac.jp