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

Ramos-Mozo, Priscila; Madrigal-Matute, Julio; Vega de Ceniga, Melina; Blanco-Colio, Luis Miguel; Meilhac, Olivier; Feldman, Laurent; Michel, Jean-Baptiste; Clancy, Paula; Golledge, Jonathan; Norman, Paul E.; Egido, Jesus; Martin-Ventura, José Luis

doi:10.1016/j.atherosclerosis.2011.11.023

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Volume 220, Issue 2 , Pages 552-556, February 2012

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

Priscila Ramos-Mozo
- Vascular Research Lab, IIS, Fundación Jimenez Diaz, Autonoma University, Madrid, Spain
Julio Madrigal-Matute
- Vascular Research Lab, IIS, Fundación Jimenez Diaz, Autonoma University, Madrid, Spain
Melina Vega de Ceniga
- Vascular Surgery, Hospital Galdakao-Usansolo, Bilbao, Spain
Luis Miguel Blanco-Colio
- Vascular Research Lab, IIS, Fundación Jimenez Diaz, Autonoma University, Madrid, Spain
Olivier Meilhac
- Inserm, U698, Univ Paris 7, CHU X-Bichat, Paris, France
Laurent Feldman
- Inserm, U698, Univ Paris 7, CHU X-Bichat, Paris, France
Jean-Baptiste Michel
- Inserm, U698, Univ Paris 7, CHU X-Bichat, Paris, France
Paula Clancy
- Vascular Biology Unit, School of Medicine and Dentistry, James Cook University, Townsville 4811, Australia
Jonathan Golledge
- Vascular Biology Unit, School of Medicine and Dentistry, James Cook University, Townsville 4811, Australia
Paul E. Norman
- School of Surgery, University of Western Australia, Perth, Australia
Jesus Egido
- Vascular Research Lab, IIS, Fundación Jimenez Diaz, Autonoma University, Madrid, Spain
José Luis Martin-Ventura
- Vascular Research Lab, IIS, Fundación Jimenez Diaz, Autonoma University, Madrid, Spain
- Corresponding author at: Vascular Research Lab, IIS, Fundación Jiménez Diaz, Autonoma University, Av. Reyes Católicos 2, 28040 Madrid, Spain. Tel.: +34 915504800; fax: +34 915442636.

Received 18 May 2011; received in revised form 26 October 2011; accepted 16 November 2011. published online 14 December 2011.

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.

Keywords: Abdominal aortic aneurysm, Biomarkers, Polymorphonuclear neutrophils, Neutrophil gelatinase-associated lipocalin, Intraluminal thrombus