Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure.
OBJECTIVE
Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2) is a glycoprotein with bacteriostatic properties. Growing evidence suggests that NGAL may also be involved in cell survival, inflammation, and matrix degradation. We therefore aimed to investigate the role of NGAL in heart failure (HF).


RESULTS
Our main findings were (i) patients with acute post-myocardial infarction (MI) HF (n = 236) and chronic HF (n = 150) had elevated serum levels of NGAL (determined by enzyme immunoassay), significantly correlated with clinical and neurohormonal deterioration, (ii) in patients with HF following acute MI, elevated NGAL levels of at baseline were associated with adverse outcomes (median of 27 months follow-up), (iii) in a rat model of post-MI HF, NGAL/lipocalin-2 gene expression was increased in the non-ischaemic part of the left ventricle primarily located to cardiomyocytes, (iv) strong NGAL immunostaining was found in cardiomyocytes within the failing myocardium both in experimental and clinical HF, (v) interleukin-1beta and agonists for toll-like receptors 2 and 4, representing components of the innate immune system, were potent inducers of NGAL/lipocalin-2 in isolated neonatal cardiomyocytes.


CONCLUSIONS
Our demonstration of enhanced systemic and myocardial NGAL expression in clinical and experimental HF further support a role for innate immune responses in the pathogenesis of HF.
Yndestad
Arne
A
Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. arne.yndestad@medisin.uio.no
Landrø
Linn
L
Ueland
Thor
T
Dahl
Christen P
CP
Flo
Trude H
TH
Vinge
Leif Erik
LE
Espevik
Terje
T
Frøland
Stig S
SS
Husberg
Cathrine
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Christensen
Geir
G
Dickstein
Kenneth
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Kjekshus
John
J
Øie
Erik
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Gullestad
Lars
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Aukrust
Pål
P