Abstract
Objective
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.
Methods
The specimens for analysis, from both thin (≤10 mm) thrombus-covered and thick (≥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.
Results
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.
Conclusion
The current study demonstrates the differentiation of protease activity within the
same AAA wall and its enhancement within the thin thrombus-covered aneurysm wall.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Role of the neutrophil in abdominal aortic aneurysm development.Cardiovasc Surg. 1993; 1: 373-376
- Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation.Circulation. 2005; 112: 232-240
- Preferential inactivation of tissue inhibitor of metalloproteinases-1 that is bound to the precursor of matrix metalloproteinase 9 (progelatinase B) by human neutrophil elastase.J Biol Chem. 1995; 270: 16518-16521
- Cellular, enzymatic, and genetic factors in the pathogenesis of abdominal aortic aneurysms.J Vasc Surg. 1989; 9: 297-304
- Elastin degradation within the abdominal aortic aneurysm wall – relationship between intramural pH and adjacent thrombus formation.Eur J Clin Invest. 2008; 38: 883-887
- Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm.Br J Surg. 2005; 92: 828-833
- Cellular content and permeability of intraluminal thrombus in abdominal aortic aneurysm.J Vasc Surg. 1997; 25: 916-926
- Mediators of neutrophil recruitment in human abdominal aortic aneurysms.Cardiovasc Res. 2009; 82: 532-541
- Differential inflammatory activity across human abdominal aortic aneurysms reveals neutrophil-derived leukotriene B4 as a major chemotactic factor released from the intraluminal thrombus.FASEB J. 2009; 23: 1376-1383
- Role of leukocyte elastase in preventing cellular re-colonization of the mural thrombus.Am J Pathol. 2004; 164: 2077-2087
- Inflammatory infiltrates and neovessels are relevant sources of MMPs in abdominal aortic aneurysm wall.Pathobiology. 2009; 76: 243-252
- Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages.J Clin Invest. 1995; 96: 318-326
- Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm.Circ Res. 2008; 102: 1368-1377
- Elastolytic and collagenolytic studies of arteries.Arch Surg. 1984; 119: 405-408
- Elastase activity: the role of elastase in aortic aneurysm formation.J Surg Res. 1982; 32: 214-217
- Hemodynamic forces regulate mural macrophage infiltration in experimental aortic aneurysms.Exp Mol Pathol. 2004; 76: 108-116
- Expression of matrix metalloproteinases and their inhibitors in aneurysms and normal aorta.Surgery. 1997; 122: 264-271
- Expression of matrix metalloproteinases and TIMPs in human abdominal aortic aneurysms.Ann Vasc Surg. 1998; 12: 221-228
- Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture.Circulation. 2006; 113: 438-445
- Matrix metalloproteinase expressions in arteriosclerotic aneurysmal disease.Vasc Endovasc Surg. 2002; 36: 1-7
- Increased tissue microarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections.Ann Thorac Surg. 2004; 78: 2106-2110
- Relationships between matrix metalloproteinases and tissue inhibitor of metalloproteinases in the wall of abdominal aortic aneurysms.Int Angiol. 2003; 22: 229-238
- Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases.Am J Pathol. 2007; 170: 809-817
- Difference in matrix-degrading protease expression and activity between thrombus-free and thrombus-covered wall of abdominal aortic aneurysm.Arterioscler Thromb Vasc Biol. 2005; 25: 1341-1346
- CT of abdominal aortic aneurysms: aneurysmal size and thickness of intra-aneurysmal thrombus as risk factors of rupture.Nippon Igaku Hoshasen Gakkai Zasshi. 1991; 51: 219-227
- Contribution of PET scanning to the evaluation of abdominal aortic aneurysm.Semin Vasc Surg. 2004; 17: 144-153
- In vivo imaging of abdominal aortic aneurysms: increased FDG uptake suggests inflammation in the aneurysm wall.J Endovasc Ther. 2008; 15: 462-467
- Aneurysmal wall calcification predicts natural history of small abdominal aortic aneurysms.Atherosclerosis. 2008; 197: 673-678
- Regional distribution of wall thickness and failure properties of human abdominal aortic aneurysm.J Biomech. 2006; 39: 3010-3016
- MR imaging of iron phagocytosis in intraluminal thrombi of abdominal aortic aneurysms in humans.Radiology. 2010; 254: 973-981
Article info
Publication history
Published online: May 31, 2010
Accepted:
April 26,
2010
Received in revised form:
April 23,
2010
Received:
November 25,
2009
Identification
Copyright
© 2010 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
