Presence of NGAL/MMP-9 complexes in human abdominal aortic aneurysms

2007 ◽  
Vol 98 (08) ◽  
pp. 427-433 ◽  
Author(s):  
Chaoyong Zhu ◽  
Angela Silveira ◽  
Anne-Louise Hemdahl ◽  
Anders Hamsten ◽  
Ulf Hedin ◽  
...  

SummaryIt has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA enlargement and rupture.The growth of theAAA is dependent on proteolytic degradation of elastin. Here, we analysed whether the neutrophil gelatinase-associated lipocalin (NGAL) is expressed within the thrombus and the aneurysm wall. NGAL can bind to metalloproteinase- 9 (MMP-9) and inhibit its degradation,thereby preserving enzymatic activity. Biopsies were obtained from thrombus- free and thrombus-covered aneurysm wall and the intraluminal thrombus from patients undergoing elective surgery for AAA. Immunohistochemistry and real-time PCR were used to study NGAL and MMP-9 expression. Immunoprecipitation, gel zymography,Western blot and ELISA were used to detect and quantify NGAL/MMP-9 complexes. NGAL was detected in the thrombus, the interface between the thrombus and the underlying wall and in the wall itself.Double staining showed that neutrophils are the major source of NGAL expression. Immunoprecipitation of MMP-9 with antibody against NGAL showed that complexes of NGAL and active MMP-9 were present in thrombus, the interface fluid and the aneurysm wall.Western blot analyses using non-reducing conditions and gel zymography demonstrated that high-molecular-weight complexes of NGAL/MMP-9 were present within the different regions.The concentration of the NGAL/MMP-9 complex was highest in the luminal part of the thrombus. In conclusion, NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. Neutrophil-derived NGAL could enhance the proteolytic activity associated with AAA, but the importance of this mechanism for aneurysm growth remains to be shown.

2019 ◽  
Vol 57 ◽  
pp. 210-219 ◽  
Author(s):  
Menno E. Groeneveld ◽  
Joyce A. Struik ◽  
René J.P. Musters ◽  
Geert J. Tangelder ◽  
Pieter Koolwijk ◽  
...  

2014 ◽  
Vol 77 (S3) ◽  
pp. 1313-1317 ◽  
Author(s):  
Georgios Karaolanis ◽  
Demetrios Moris ◽  
Viktoria-Varvara Palla ◽  
Euridiki Karanikola ◽  
Chris Bakoyiannis ◽  
...  

Vascular ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Tom W.G. Carrell ◽  
Kevin G. Burnand ◽  
Nuala A. Booth ◽  
Julia Humphries ◽  
Alberto Smith

This study examined whether intraluminal thrombus in abdominal aortic aneurysms (AAAs) is a source of fibrinolytic activity and proteolysis that could weaken the aneurysm wall. Plasmin, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) activity, plasminogen activator inhibitor 1 (PAI-1), and α2-antiplasmin (α2AP) antigen were measured in the AAA wall and juxtamural and luminal aspects of intraluminal thrombus in 18 patients. The aneurysm wall contained 100-fold higher tPA activity (1.06 ± 0.34 [standard error of measurement] U/mg soluble protein) compared with juxtamural thrombus (JMT) (0.011 ± 0.001 ) and luminal thrombus (LT) (0.01 ± 0.001) ( p < .00001) and over 6-fold higher uPA activity (29.3 ± 3.4 IU/mg compared with the JMT (4.3 ± 2.4, p = .00024) and LT (7.9 ± 1.76, p = .0005). The LT had significantly lower levels of PAI-1 (1.26 ± 0.34 ng/mg) than the AAA wall (2.08 ± 0.51, p = .04) and the JMT (3.94 ± 0.85, p = .007). The levels of α2AP in the wall (19.4 ± 3.1 ng/mg) were lower than in the JMT or LT (43.0 ± 7.9 ng/mg, p = .013, and 47.6 ± 6.0 ng/mg, p = .002, respectively). There was no significant difference, however, in plasmin activity among the AAA wall, JMT, and LT. There were significant amounts of latent gelatinase B (matrix metalloproteinase [MMP]-9) in the AAA, JMT, and LT. Mean levels of activated MMP-9 activity were similar in the AAA, JMT, and LT. Plasmin activation of MMPs at the interface between intraluminal thrombus and the aneurysm wall may enhance proteolysis and accelerate aneurysm expansion.


2000 ◽  
Author(s):  
Mano J. Thubrikar ◽  
Michel Labrosse ◽  
Jihad Al-Soudi ◽  
Brett Fowler ◽  
Francis Robicsek

Abstract Abdominal aortic aneurysms (AAA) rupture when the aortic wall cannot withstand the stresses and strains induced by the pulsatile blood pressure. In recent years, different mechanical models of aneurysms have been presented (Vorp et al., 1998, Di Martino et al., 1998, Thubrikar et al., 1999). Although powerful modeling tools such as finite elements are available, there is still a need for experimental data concerning the mechanical properties of the aneurysm wall.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Joy Roy ◽  
Angela Silveira ◽  
Moritz Liljeqvist Lindquist ◽  
Maggie Folkesson ◽  
Siw Frebelius ◽  
...  

Introduction: Abdominal Aortic Aneurysms (AAA) often contain an intraluminal thrombus (ILT). AAA diameter and ILT volume are associated with growth of the aneurysm. Neutrophils, present in the ILT, contain elastase (NE). NE activity leads to production of fibrin degradation products (FDPs) with a specific epitope [[Unable to Display Character: &#8211;]] XDP. The present study evaluates NE-derived FDPs in aneurysm patients scheduled for elective aortic repair. The purpose of the study is to introduce an additional bio-marker for presence of AAA and possibly risk of rupture by measuring levels of NE derived FDPs in plasma of patients with AAA. Materials and Methods: 42 male patients, undergoing aortic repair for AAA were included. As controls, we collected blood samples from 42 men who attended an AAA screening program but had no AAAs on ultrasound. Computed Tomography (CT) images were available for 34 AAA patients and analyzed using A4 Clinics software (VASCOPS, Austria). Patient demographics, maximum diameter, aortic volume and ILT volume were recorded. Peak wall stress (PWS), peak wall rupture index (PWRI) and mean ILT stress were estimated by Finite Element Analysis using the A4 Clinics software. Plasma levels of elastase digests of cross-linked fibrin (E-XDP) were determined with a sandwich ELISA. Results: E-XDP levels were higher in AAA patients than in age-matched controls (8.5 vs 1.2 U/ml, p<0.0001). E-XDP levels correlated with ILT volume (r = 0.64, p<0.0001), aortic volume (r = 0.64, p<0.0001) and maximum diameter (r = 0.59, p=0.0003). AAA patients with other concomitant peripheral aneurysms had higher E-XDP levels than those with only an AAA (13.6 vs 6.8 U/ml, p=0.028). PWS, PWRI and bleeding signs in the thrombus did not significantly affect E-XDP levels. Interestingly, the mean ILT stress correlated significantly to E-XDP levels (r= 0.45, p=0.008). Conclusions: The study shows that it is feasible to measure E-XDP levels in plasma of patients with AAA and that E-XDP correlates with ILT volume and mean ILT stress. These results support the notion that the resident neutrophils in the ILT can actively lyse fibrin in the ILT, which may decrease ILT strength. E-XDP holds potential as a biomarker of the ILT in AAA patients and needs to be further investigated in AAA rupture risk assessment.


2018 ◽  
Vol 38 (Suppl_1) ◽  
Author(s):  
Moritz Lindquist Liljeqvist ◽  
Rebecka Hultgren ◽  
Christina Villard ◽  
Malin Kronqvist ◽  
Per Eriksson ◽  
...  

1998 ◽  
Vol 18 (2) ◽  
pp. 168-177 ◽  
Author(s):  
Ulrika Enemark ◽  
Carl H. Lyttkens ◽  
Thomas Troëng ◽  
Henrik Weibull ◽  
Jonas Ranstam

A growing empirical literature has investigated attitudes towards discounting of health benefits with regard to social choices of life-saving and health-improving measures and individuals' time preferences for the management of their own health. In this study, the authors elicited the time preferences of vascular surgeons in the context of management of small abdominal aortic aneurysms, for which the choice between early elective surgery and watchful waiting is not straightforward. They interviewed 25 of a random sample of 30 Swedish vascular surgeons. Considerable variation in the time preferences was found in the choices between watchful waiting and surgical intervention among the otherwise very homogeneous group of surgeons. The discount rates derived ranged from 5.3% to 19.4%. The median discount rate (10.4%) is similar to those usually reported for social choices concerning life-saving measures. The surgeons who were employed in university hospitals had higher discount rates than did their colleagues in county and district hospitals.


Sign in / Sign up

Export Citation Format

Share Document