Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in hearts of rats with autoimmune myocarditis and in human myocarditis

Circ J. 2010 Mar;74(3):523-30. doi: 10.1253/circj.cj-09-0485. Epub 2010 Jan 7.

Abstract

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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics*
  • Acute-Phase Proteins / metabolism
  • Aged
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / physiopathology*
  • Disease Models, Animal
  • Female
  • Fibroblasts / physiology
  • Gene Expression / physiology
  • Heart Failure / immunology
  • Heart Failure / physiopathology*
  • Humans
  • Immunization
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics
  • Lipocalin-2
  • Lipocalins / blood
  • Lipocalins / genetics*
  • Lipocalins / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Myocarditis / immunology
  • Myocarditis / physiopathology*
  • Myocytes, Cardiac / physiology
  • Myosins / immunology
  • Natriuretic Peptide, Brain / blood
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Rats
  • Swine
  • Young Adult

Substances

  • Acute-Phase Proteins
  • Interleukin-1beta
  • LCN2 protein, human
  • Lcn2 protein, rat
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • natriuretic peptide precursor type B, rat
  • Natriuretic Peptide, Brain
  • Matrix Metalloproteinase 9
  • Myosins