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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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1437-4331
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Volume 56, Issue 1

Issues

NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis

Wolf Eilenberg
  • Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria
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/ Stefan Stojkovic
  • Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
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/ Alexandra Kaider
  • Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
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/ Nicolas Kozakowski / Christoph M. Domenig
  • Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria
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/ Christopher Burghuber
  • Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria
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/ Josif Nanobachvili
  • Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria
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/ Kurt Huber
  • 3rd Medical Department for Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria
  • Sigmund Freud Private University, Medical School, Vienna, Austria
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/ Markus Klinger
  • Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria
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/ Christoph Neumayer
  • Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria
  • Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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/ Ihor Huk
  • Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria
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/ Johann Wojta
  • Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
  • Core Facilities, Medical University of Vienna, Vienna, Austria
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/ Svitlana Demyanets
  • Corresponding author
  • Department of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria, Phone: +43 1 40400/53550, Fax: +43 1 40400/73587
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Published Online: 2017-06-26 | DOI: https://doi.org/10.1515/cclm-2017-0156

Abstract

Background:

Neutrophil gelatinase associated lipocalin (NGAL) is expressed in atherosclerotic lesions and was recently implicated in the pathogenesis of cardiovascular pathologies. Statins are known to exert stabilizing effects on atherosclerotic plaque. The aims of our study were (1) to investigate the association of serum NGAL and metalloproteinase (MMP)-9/NGAL complex with the vulnerability of the atherosclerotic plaque, and (2) to reveal the effects of statin treatment on circulating NGAL and MMP-9/NGAL levels in patients with carotid artery stenosis.

Methods:

We examined the levels of NGAL and MMP-9/NGAL in blood samples from 136 patients with carotid artery stenosis by specific enzyme-linked immunosorbent assays.

Results:

Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of American Heart Association [AHA]), displayed the highest levels of NGAL (both p<0.0001) and MMP-9/NGAL complex (p=0.0004 and p=0.004, respectively). Moreover, patients with symptomatic carotid atherosclerosis had significantly higher NGAL levels compared to asymptomatic patients (p=0.0007). The statin-treated group (n=108) demonstrated lower NGAL (73.9 vs. 128.0 μg/L, p<0.0001) and MMP-9/NGAL (28.9 vs. 40.6 μg/L, p=0.046) as compared to the non-statin group (n=28). Furthermore, in multivariate regression analysis NGAL, but not MMP-9/NGAL levels, were independently associated with symptomatic carotid artery stenosis. In addition, statin treatment was independently associated with lower NGAL levels.

Conclusions:

Circulating NGAL and MMP-9/NGAL are associated with plaque vulnerability in patients with carotid artery stenosis. Statin treatment could contribute to plaque stabilization by reducing circulating NGAL and MMP-9/NGAL levels.

Keywords: biomarker; carotid artery stenosis; neutrophil gelatinase associated lipocalin; plaque vulnerability; statins

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About the article

Corresponding author: Svitlana Demyanets, MD, PhD, Department of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria, Phone: +43 1 40400/53550, Fax: +43 1 40400/73587

Wolf Eilenberg and Stefan Stojkovic contributed equally to this work.


Received: 2017-02-23

Accepted: 2017-05-13

Published Online: 2017-06-26

Published in Print: 2017-11-27


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Financial support: Svitlana Demyanets has received grant support from the Herzfelder’sche Familienstiftung (Vienna, Austria). The other authors have no conflicts to report. Furthermore, this work was supported by the Association for the Promotion of Research in Atherosclerosis, Thrombosis and Vascular Biology.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 1, Pages 147–156, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0156.

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