Intraluminal Thrombus has a Selective Influence on Matrix Metalloproteinases and Their Inhibitors (Tissue Inhibitors of Matrix Metalloproteinases) in the Wall of Abdominal Aortic Aneurysms Junaid A. Khan, 1 M.N.A. Abdul Rahman, 1 F.A.K. Mazari, 1 Y. Shahin, 1 G. Smith, 1 L. Madden, 2 M.J. Fagan, 3 J. Greenman, 2 P.T. McCollum, 1 and I.C. Chetter, 1 Hull, United Kingdom Background: 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. Methods: 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. Results: 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 demon- strated a positive correlation with ILT thickness, although not statistically significant. Conclusion: 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 implica- tions for AAA expansion and eventual rupture. INTRODUCTION The cellular components of blood vessels are sup- ported and organized by a complex structure of collagens, elastins, laminins, fibronectins, and proteoglycans. 1 In the aorta, elastic fibers and fibrillar collagens are the main determinants of its mechanical properties. Loss of elastin is one of the most consistent findings in the early steps of aneu- rysm formation, 2 which occurs when there is an imbalance between extracellular matrix (ECM) synthesis and degradation. 2 The asymmetric shape of abdominal aortic aneu- rysm (AAA) causes turbulence and stagnation in the blood flow, resulting in endothelial injury, which promotes formation of intraluminal thrombus (ILT). ILT is present in 75% of all AAAs. 3 ILT contains many living cells, including macrophages and neutrophils, 4 which may act as a source of matrix metalloproteinases (MMPs) and tissue inhib- itors of matrix metalloproteinases (TIMPs). 5 An ex vivo analysis of ILT taken from patients undergoing elective AAA repair found a higher 1 Academic Vascular Surgical Unit, Hull York Medical School and University of Hull, Hull, UK. 2 Postgraduate Medical Institute, University of Hull, Hull, UK. 3 Department of Engineering, University of Hull, Hull, UK. Correspondence to: Junaid A. Khan, MBBS, BSc, FCPS, MRCS, Academic Vascular Surgical Unit, University of Hull, Hull Royal Infir- mary, HU3 2JZ Hull, UK; E-mail: junaid.khan@hey.nhs.uk Ann Vasc Surg 2012; 26: 322–329 DOI: 10.1016/j.avsg.2011.08.015 Ó Annals of Vascular Surgery Inc. Published online: February 6, 2012 322