The Potential Role of Neutrophil Gelatinase-Associated Lipocalin in the Development of Abdominal Aortic Aneurysms.
Adult
Aged
Aged, 80 and over
Aorta, Abdominal
/ chemistry
Aortic Aneurysm, Abdominal
/ blood
Aortic Rupture
/ blood
Apoptosis
Biomarkers
/ blood
Caspase 3
/ analysis
Dilatation, Pathologic
Disease Progression
Female
Humans
Lipocalin-2
/ blood
Male
Matrix Metalloproteinase 9
/ analysis
Middle Aged
Oxidative Stress
Retrospective Studies
Tyrosine
/ analogs & derivatives
Up-Regulation
Vascular Remodeling
Journal
Annals of vascular surgery
ISSN: 1615-5947
Titre abrégé: Ann Vasc Surg
Pays: Netherlands
ID NLM: 8703941
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
02
08
2018
revised:
14
11
2018
accepted:
27
11
2018
pubmed:
27
1
2019
medline:
18
6
2019
entrez:
27
1
2019
Statut:
ppublish
Résumé
In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture. In this observational study, aneurysm tissue and blood of ruptured (n = 13) AAA patients were investigated versus nonruptured (n = 26) patients. Nondilated aortas (n = 5) from deceased patients and venous blood from healthy volunteers (n = 10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively. NGAL (in μg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P < 0.01) and 14 (range 12-22) in controls (P < 0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P = 0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs = 0.80, P < 0.01), MMP-9 (Rs = 0.56, P = 0.02), and caspase-3 (Rs = 0.75, P = 0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P = 0.34 and P = 0.95, respectively). This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.
Sections du résumé
BACKGROUND
BACKGROUND
In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture.
METHODS
METHODS
In this observational study, aneurysm tissue and blood of ruptured (n = 13) AAA patients were investigated versus nonruptured (n = 26) patients. Nondilated aortas (n = 5) from deceased patients and venous blood from healthy volunteers (n = 10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively.
RESULTS
RESULTS
NGAL (in μg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P < 0.01) and 14 (range 12-22) in controls (P < 0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P = 0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs = 0.80, P < 0.01), MMP-9 (Rs = 0.56, P = 0.02), and caspase-3 (Rs = 0.75, P = 0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P = 0.34 and P = 0.95, respectively).
CONCLUSIONS
CONCLUSIONS
This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.
Identifiants
pubmed: 30684630
pii: S0890-5096(19)30030-5
doi: 10.1016/j.avsg.2018.11.006
pii:
doi:
Substances chimiques
Biomarkers
0
LCN2 protein, human
0
Lipocalin-2
0
3-nitrotyrosine
3604-79-3
Tyrosine
42HK56048U
CASP3 protein, human
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
MMP9 protein, human
EC 3.4.24.35
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
210-219Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.