Intraluminal Thrombus Enhances Proteolysis in Abdominal Aortic Aneurysms

Vascular ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Tom W.G. Carrell ◽  
Kevin G. Burnand ◽  
Nuala A. Booth ◽  
Julia Humphries ◽  
Alberto Smith
Keyword(s):  
Plasminogen Activator ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Plasmin Activity ◽  
Plasminogen Activator Inhibitor 1 ◽  
Intraluminal Thrombus ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Pai 1

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.

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 ◽  
...  
Keyword(s):  
Elective Surgery ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Intraluminal Thrombus ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Reducing Conditions ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Aneurysm Growth ◽  
Neutrophil Gelatinase

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.

High levels of homocysteine, lipoprotein (a) and plasminogen activator inhibitor-1 are present in patients with abdominal aortic aneurysm

2005 ◽  
Vol 94 (11) ◽  
pp. 1094-1098 ◽  
Author(s):  
Rossella Marcucci ◽  
Betti Giusti ◽  
Giovanni Pratesi ◽  
Barbara Lari ◽  
Ilaria Sestini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Factor V Leiden Mutation ◽  
Lipoprotein A ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryOver the last few years, there has been increasing interest in the investigation of the pathogenesis of AAA, and a role for some novel risk factors, in particular thrombophilic risk factors, has been suggested. The aim of this study was to evaluate a number of thrombophilic parameters in a large group of patients with AAA. In 438 patients with AAA, and in 438 healthy subjects, selected to be comparable for age and gender with patients and without instrumental evidence of AAA, a pattern of thrombophilic parameters [homocysteine (Hcy), lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), anticardiolipin antibodies (ACA), MTHFR C677T polymorphism, prothrombin gene G20210A variant and Factor V Leiden mutation] has been evaluated. A significant difference for Hcy, PAI-1 and Lp(a) plas-After adjustment for the traditional cardiovascular risk factors, a significant increased risk of having AAA has been observed for high levels of Hcy (OR: 7.8; p<0.0001), Lp(a) (OR: 2.4; p<0.0001) and PAI-1 (OR:3.2;p<0.0001). The association has been confirmed after exclusion of patients with other localization of atherosclerosis. Moreover, a significant association between larger abdominal aortic diameters and the number of thrombophilic parameters has been reported (r = 0.13; p = 0.005). In conclusion, a significant association between abnormal levels of some metabolic parameters related to thrombosis such as Hcy, Lp(a) and PAI-1 and AAA has been observed.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Efficacy and safety of doxycycline for the management of small abdominal aortic aneurysms- a meta analysis

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
D Rocha Castellanos ◽  
A Lopez Mendez ◽  
M Fernando Perez Paz ◽  
S Pothuru ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Abdominal Aortic Aneurysms ◽  
Abdominal Aortic Aneurysm Repair ◽  
Mean Difference ◽  
Aortic Aneurysms ◽  
Efficacy And Safety ◽  
Funding Sources ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Aneurysm Repair

Abstract Funding Acknowledgements Type of funding sources: None. Background- Patients with small Abdominal Aortic Aneurysms are managed with surveillance as there is currently insufficient evidence to recommend surgical aneurysm repair. Hence, there is a dire need and interest in pharmacotherapy like tetracycline antibiotics to reduce the need for aneurysm repair. Purpose- To determine the efficacy and safety of doxycycline in the management of small abdominal aortic aneurysms. Methods- Electronic databases (PubMed, Scopus, Embase, Cochrane) were searched until 25th November 2020.The primary outcomes were the mean difference (MD) in aneurysm diameter and the odds ratio (OR) calculated to compare the number of individuals referred to Abdominal aortic aneurysm repair in each group. Results- A total of three studies with 572 participants (Doxycycline = 290; Placebo = 282 ) were included in our analysis. Average follow up was a period of 18 months. For AAA expansion, the combined results demonstrated a statistically significant mean difference in expansion rates favoring the placebo groups over the intervention (WMD-0.75, 95%CI 0.12-1.38; p = 0.02;I2 = 0%) There was no statistically significant difference in the efficacy and safety of doxycycline as opposed to placebo groups for referral to AAA surgery (OR 1.01, 95%CI 0.61-1.69; p = 0.96, I2 = 0%) and all-cause mortality(OR 0.51; 95%CI 0.18-1.43; p = 0.20, I2 =0%) Conclusion- Amongst patients with small abdominal aortic aneurysms, doxycycline did not significantly reduce aneurysm growth. Abstract Figure. A) AAA expansion B)Surgery C)Mortality

Material Properties of Abdominal Aortic Aneurysm Wall From Uniaxial Tests

2000 ◽  
Author(s):  
Mano J. Thubrikar ◽  
Michel Labrosse ◽  
Jihad Al-Soudi ◽  
Brett Fowler ◽  
Francis Robicsek
Keyword(s):  
Experimental Data ◽  
Material Properties ◽  
Aortic Wall ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Modeling Tools ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Abdominal Aortic Aneurysm Wall ◽  
Mechanical Models

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.

Abstract 261: Neutrophil Elastase Derived Fibrin Degradation Products are Increased in the Plasma of Patients with Abdominal Aortic Aneurysms and Correlate to the Intraluminal Thrombus Volume

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Joy Roy ◽  
Angela Silveira ◽  
Moritz Liljeqvist Lindquist ◽  
Maggie Folkesson ◽  
Siw Frebelius ◽  
...  
Keyword(s):  
Degradation Products ◽  
Sandwich Elisa ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Maximum Diameter ◽  
Intraluminal Thrombus ◽  
Fibrin Degradation Products ◽  
Aortic Repair ◽  
Abdominal Aortic ◽  
Risk Of Rupture

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.

Abstract 725: Effect of Intraluminal Thrombus on the Transcriptome of the Tunica Media and Adventitia in Abdominal Aortic Aneurysms

2018 ◽  
Vol 38 (Suppl_1) ◽  
Author(s):  
Moritz Lindquist Liljeqvist ◽  
Rebecka Hultgren ◽  
Christina Villard ◽  
Malin Kronqvist ◽  
Per Eriksson ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Intraluminal Thrombus ◽  
Tunica Media ◽  
Abdominal Aortic
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