title: Intraluminal abdominal aortic aneurysm thrombus is associated with disruption of wall integrity.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. d.koole@umcutrecht.nl
authors.forename: Dave
authors.initials: D
authors.lastname: Koole
authors.forename: Herman J A
authors.initials: HJ
authors.lastname: Zandvoort
authors.forename: Arjan
authors.initials: A
authors.lastname: Schoneveld
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Jan A
authors.initials: JA
authors.lastname: Vos
authors.forename: Luuk L
authors.initials: LL
authors.lastname: van den Hoogen
authors.forename: Jean-Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Joost A
authors.initials: JA
authors.lastname: van Herwaarden
mesh_terms: D000368:Aged; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology*; D001019:Aortic Rupture / Q000201:enzymology / Q000473:pathology; D001027:Aortography / Q000379:methods; D017209:Apoptosis; D001706:Biopsy; D002401:Cathepsin B / Q000032:analysis; D002403:Cathepsins / Q000032:analysis; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D016014:Linear Models; D015227:Lipid Peroxidation; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D015999:Multivariate Analysis; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D015588:Observer Variation; D009195:Peroxidase / Q000032:analysis; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology*; D014057:Tomography, X-Ray Computed
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D003094:Collagen; D004549:Elastin; D009195:Peroxidase; D002403:Cathepsins; C533912:CTSB protein, human; D002401:Cathepsin B; C028217:cathepsin S; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9