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 ◽  
...  
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.


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.


Author(s):  
Christopher A. Basciano ◽  
Julie H. Y. Ng ◽  
Ender A. Finol ◽  
Clement Kleinstreuer

Abdominal aortic aneurysms (AAAs) are local dilations of the aorta below the renal arteries where the lumen diameter is ≥ 1.5 times the normal diameter of the healthy blood vessel. Ruptured aneurysms are the 13th leading cause of death in the US [1]. In approximately 75% of all AAAs, a particle-deposition layer forms adjacent to the arterial wall within the lumen called the intra-luminal thrombus (ILT). The thrombus composition has been shown to be a fibrin structure composed of blood cells, platelets, blood proteins, and other cellular debris [2]. Additionally, Yamazumi et al. [3] have presented data that suggest AAA morphology is associated with an elevated state of blood coagulation and fibrinolysis within the aneurysm.


2016 ◽  
Vol 64 (2) ◽  
pp. 543-544
Author(s):  
Jeffrey D. Crawford ◽  
Stephen J. Haller ◽  
Gregory J. Landry ◽  
Cherrie Abraham ◽  
Gregory L. Moneta ◽  
...  

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