Intraluminal abdominal aortic aneurysm thrombus is associated with disruption of wall integrity.

An association of intraluminal thrombus (ILT) with abdominal aortic aneurysm (AAA) growth has been suggested. Previous in vitro experiments have demonstrated that aneurysm-associated thrombus may secrete proteolytic enzymes and may develop local hypoxia that might lead to the formation of tissue-damaging reactive oxygen species. In this study, we assessed the hypothesis that ventral ILT thickness is associated with markers of proteolysis and with lipid oxidation in the underlying AAA vessel wall. Ventral AAA tissue was collected from asymptomatic patients at the site of maximal diameter during open aneurysm repair. Segments were divided, one part for biochemical measurements and one for histologic analyses. We measured total cathepsin B, cathepsin S levels, and matrix metalloproteinase (MMP)-2 and MMP-9 activity. Myeloperoxidase and thiobarbituric acid reactive substances were determined as measures of lipid oxidation. Histologic segments were analyzed semiquantitatively for the presence of collagen, elastin, vascular smooth muscle cells (VSMCs), and inflammatory cells. Preoperative computed tomography angiography scans of 83 consecutive patients were analyzed. A three-dimensional reconstruction was obtained, and a center lumen line of the aorta was constructed. Ventral ILT thickness was measured in the anteroposterior direction at the level of maximal aneurysm diameter on the orthogonal slices. Ventral ILT thickness was positively correlated with aortic diameter (r=0.25; P=.02) and with MMP-2 levels (r=0.27; P=.02). No biochemical correlations were observed with MMP-9 activity or cathepsin B and S expression. No correlation between ventral ILT thickness and myeloperoxidase or thiobarbituric acid reactive substances was observed. Ventral ILT thickness was negatively correlated with VSMCs (no staining, 18.5 [interquartile range, 12.0-25.5] mm; minor, 17.6 [10.7-22.1] mm; moderate, 14.5 [4.6-21.7] mm; and heavy, 8.0 [0.0-12.3] mm, respectively; P=.01) and the amount of elastin (no staining, 18.6 [12.2-30.0] mm; minor, 16.5 [9.0-22.1] mm; moderate, 11.7 [2.5-15.3] mm; and heavy 7.7 [0.0-7.7] mm, respectively; P=.01) in the medial aortic layer. ILT thickness appeared to be associated with VSMCs apoptosis and elastin degradation and was positively associated with MMP-2 concentrations in the underlying wall. This suggests that ILT thickness affects AAA wall stability and might contribute to AAA growth and rupture. ILT thickness was not correlated with markers of lipid oxidation.

Koole D ，Zandvoort HJ ，Schoneveld A ，Vink A ，Vos JA ，van den Hoogen LL ，de Vries JP ，Pasterkamp G ，Moll FL ，van Herwaarden JA ... -  《-》

Magnetic resonance imaging assessment of proteolytic enzyme concentrations and biologic properties of intraluminal thrombus in abdominal aortic aneurysms.

The aim of the study was to determine whether magnetic resonance imaging (MRI) can be used in assessment of biologic activity of intraluminal thrombus (ILT) and proteolytic processes of the abdominal aortic aneurysm wall. Using MRI, 50 patients with asymptomatic infrarenal abdominal aortic aneurysm were analyzed at the maximum aneurysm diameter on T1-weighted images in the arterial phase after administration of contrast material. Relative ILT signal intensity (SI) was determined as the ratio between ILT SI and psoas muscle SI. During surgery, the full thickness of the ILT and the adjacent part of the aneurysm wall were harvested at the maximal diameter for biochemical analysis. The concentrations of matrix metalloproteinase 9 and neutrophil elastase (NE/ELA) were analyzed in harvested thrombi, and the concentrations of collagen type III, elastin, and proteoglycans were analyzed in harvested aneurysm walls. A significant positive correlation was found between the NE/ELA concentration of the ILT and the relative SI (ρ = 0.309; P = .029). Furthermore, a negative correlation was observed between the elastin content of the aneurysm wall and the relative SI (ρ = -0.300; P = .034). No correlations were found between relative SI and concentration of matrix metalloproteinase 9, NE/ELA, collagen type III, or proteoglycan 4 in the aneurysm wall. These findings indicate a potential novel use of MRI in prediction of thrombus proteolytic enzyme concentrations and the extracellular matrix content of the aneurysm wall, thus providing additional information for the risk of potential aneurysm rupture.

Sladojevic M ，Stanojevic Z ，Koncar I ，Zlatanovic P ，Vidicevic S ，Tosic J ，Isakovic A ，Markovic M ，Davidovic L ... -  《-》

Diameter-related variations of geometrical, mechanical, and mass fraction data in the anterior portion of abdominal aortic aneurysms.

Maximum aortic diameter is an important measure in rupture prediction of abdominal aortic aneurysms (AAAs). Analyzing the variations of geometrical, material, and biochemical properties with increased AAA diameters advances understanding of the effect of lesion enlargement on patient specific vascular properties. 96 AAA samples were harvested during open surgical aneurysm repair. Geometrical factors such as the maximum intraluminal thrombus (ILT) thickness, wall thickness, and AAA expansion rate were measured. Biaxial extension and peeling tests were performed to characterize the biaxial mechanical responses and to quantify the dissection properties of aneurysmal tissue. Mass fraction analysis quantified the dry weight percentages of elastin and collagen within the AAA wall. Linear regression models were used to correlate geometrical, mechanical, and mass fraction data with maximum AAA diameter. Both ILT thickness and AAA expansion rate increased and were positively correlated with maximum AAA diameter, while there was a slight increase in wall thickness for AAAs with a larger maximum diameter. For the biaxial mechanical responses, mean peak stretches and maximum tangential moduli in the circumferential and longitudinal axes did not correlate with maximum AAA diameters. However, the quantified energy to propagate tissue dissections within intima-media composites showed a significant inverse correlation with maximum AAA diameter. Elastin content decreased significantly with increasing AAA diameter. Larger AAA diameters are associated with thicker ILTs, higher AAA expansion rates, and pronounced elastin loss, and may also lead to a higher propensity for tissue dissection and aneurysm rupture.

Tong J ，Cohnert T ，Holzapfel GA 《-》

Enhanced matrix-degrading proteolytic activity within the thin thrombus-covered wall of human abdominal aortic aneurysms.

The maintenance of an arterial elastin's integrity is essential in the prevention of abdominal aortic aneurysm (AAA) development. So far, the effect of intraluminal thrombus (ILT) thickness on the elastolytic activity within the AAA wall has not been studied. In the present study the hypothesis that thin thrombus is associated with enhanced proteolytic activity within human AAA wall was investigated. The specimens for analysis, from both thin (< or = 10 mm) thrombus-covered and thick (> or = 25 mm) thrombus-covered wall, had been taken from 40 patients undergoing elective repair of AAA. We evaluated neutrophil elastase activity with the enzymatic assay. Concentrations of active matrix metalloproteinase-9 (MMP-9), total matrix metalloproteinase-8 (MMP-8), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were measured by ELISA. Biochemical parameters were compared with the Wilcoxon signed-rank test. Statistical analysis showed that the activity of elastase (P<0.0001) as well as concentrations of active MMP-9 (P=0.001), total MMP-8 (P<0.0001) and active MMP-9/total TIMP-1 ratio (P=0.002) were significantly higher in the thin thrombus-covered wall. Furthermore the TIMP-1 was found to have a lower concentration in the thin thrombus-covered in comparison with the thick thrombus-covered wall (P=0.003). There was a significant positive correlation between measurements in AAA wall sites with thin and thick thrombus for elastase, TIMP-1, MMP-9/TIMP-1 ratio, and a borderline correlation was observed for MMP-8. Active MMP-9 concentration did not correlate between sites. The current study demonstrates the differentiation of protease activity within the same AAA wall and its enhancement within the thin thrombus-covered aneurysm wall.

Wiernicki I ，Stachowska E ，Safranow K ，Cnotliwy M ，Rybicka M ，Kaczmarczyk M ，Gutowski P ... -  《-》

Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms.

The influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall. Thirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms. There was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant. In this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture.

Khan JA ，Abdul Rahman MN ，Mazari FA ，Shahin Y ，Smith G ，Madden L ，Fagan MJ ，Greenman J ，McCollum PT ，Chetter IC ... -  《-》