Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in hearts of rats with autoimmune myocarditis and in human myocarditis.
BACKGROUND
Lipocalin-2/neutrophil gelatinase-B associated lipocalin (Lcn2/NGAL) is involved in the transport of iron and seems to play an important role in inflammation. A recent study has reported that it is also expressed in the failing heart and may be a biomarker not only for renal failure but also for heart failure. Because Lcn2/NGAL is thought to be induced by interleukin-1, it might be strongly induced in the presence of myocarditis.


RESULTS
This study investigated the expression of Lcn2/NGAL in rat experimental autoimmune myocarditis (EAM) and in human myocarditis. In EAM hearts, the expression of Lcn2/NGAL was markedly increased (>100-fold at an early stage), and in human myocarditis it was also highly expressed compared with non-inflammatory failing hearts. Lcn2/NGAL expressing cells in hearts with EAM and human myocarditis were identified as cardiomyocytes, vascular wall cells, fibroblasts and neutrophils. Lcn2/NGAL in EAM rats was also expressed in the liver. Plasma Lcn2/NGAL levels abruptly increased at an early stage of EAM, and high levels were initially sustained during the inflammatory stage, then decreased with recovery. In contrast, levels of B-type natriuretic peptide increased only slowly as the disease progressed.


CONCLUSIONS
Cardiomyocytes, vascular wall cells and fibroblasts in myocarditis strongly express Lcn2/NGAL via proinflammatory cytokines.
Ding
Limin
L
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Japan
Hanawa
Haruo
H
Ota
Yoshimi
Y
Hasegawa
Go
G
Hao
Kazuhisa
K
Asami
Fuyuki
F
Watanabe
Ritsuo
R
Yoshida
Tsuyoshi
T
Toba
Ken
K
Yoshida
Kaori
K
Ogura
Minako
M
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006333:Heart Failure / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007114:Immunization; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009205:Myocarditis / Q000276:immunology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology; D009218:Myosins / Q000276:immunology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013552:Swine; D055815:Young Adult
D000209:Acute-Phase Proteins; D053583:Interleukin-1beta; C489506:LCN2 protein, human; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C495963:natriuretic peptide precursor type B, rat; D020097:Natriuretic Peptide, Brain; D020780:Matrix Metalloproteinase 9; D009218:Myosins