期刊
EUROPEAN HEART JOURNAL
卷 30, 期 10, 页码 1229-1236出版社
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehp088
关键词
Heart failure; Lipocalin; Innate immunity; Matrix metalloproteinase
资金
- Norwegian Council of Cardiovascular Research
- University of Oslo
- Medinnova Foundation, Helse Sor
- Rikshospitalet University Hospital
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). 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-1 beta 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. 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.
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