Increased plasma levels of NGAL, a marker of neutrophil activation, in patients with abdominal aortic aneurysm

Atherosclerosis. 2012 Feb;220(2):552-6. doi: 10.1016/j.atherosclerosis.2011.11.023. Epub 2011 Nov 25.

Abstract

Objective: Neutrophil gelatinase-associated lipocalin (NGAL) plasma concentrations have been associated with cardiovascular diseases. We aimed to assess the association of NGAL with abdominal aortic aneurysm (AAA).

Methods: NGAL concentrations were analyzed by Western blotting in conditioned medium of polymorphonuclear neutrophils (PMNs) from AAA patients (n=22) and controls (n=11), and also in aortic biopsies from AAA patients and healthy controls (n=10). Plasma NGAL concentrations were measured by ELISA in three groups of subjects from France (n=60), Spain (n=75) and Australia (n=100) and associated with AAA presence and growth.

Results: PMNs isolated from AAA patients secreted significantly greater amounts of NGAL than PMNs from controls. Luminal thrombus released large amounts of NGAL compared to abluminal AAA thrombus, AAA wall and healthy aortic media. Plasma NGAL concentrations were significantly higher in patients with AAA than controls from France [115 (78-200) vs. 94 (72-114) ng/ml, p<0.001]. NGAL plasma concentrations in AAA patients from Spain correlated with other markers of thrombus activity (plasmin-antiplasmin complexes and D-dimer). Furthermore, a positive correlation between plasma NGAL and retrospective AAA growth (rho=0.4, p=0.01) was observed, which remained significant after adjusting for other risk factors. Plasma NGAL was only weakly associated with prospective growth in both Spanish and Australian patients.

Conclusions: NGAL is released by PMNs and by the luminal part of AAA thrombus. NGAL plasma levels were increased in AAA patients compared with healthy subjects and correlated with retrospective AAA growth. Further studies in larger subjects groups are needed to confirm the association between NGAL and AAA presence and growth.

Trial registration: ClinicalTrials.gov NCT00430820.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Aortic Aneurysm, Abdominal / blood*
  • Aortic Aneurysm, Abdominal / immunology
  • Aortic Aneurysm, Abdominal / pathology
  • Australia
  • Biomarkers / blood
  • Biopsy
  • Blotting, Western
  • Case-Control Studies
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • France
  • Humans
  • Linear Models
  • Lipocalin-2
  • Lipocalins / blood*
  • Male
  • Multivariate Analysis
  • Neutrophil Activation*
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Prospective Studies
  • Proto-Oncogene Proteins / blood*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Spain
  • Thrombosis / metabolism
  • Up-Regulation

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Culture Media, Conditioned
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins

Associated data

  • ClinicalTrials.gov/NCT00430820