European Journal of Clinical Investigation (2004) 34, 513–514 © 2004 Blackwell Publishing Ltd Blackwell Publishing, Ltd. Letter to the Editor Gradient of proteolytic enzymes, their inhibitors and matrix proteins expression in a ruptured abdominal aortic aneurysm O. D. Defawe, A. Colige, C. A. Lambert, P. Delvenne, Ch. M. Lapière, R. Limet, B. V. Nusgens and N. Sakalihasan University of Liège, Liège, Belgium Eur J Clin Invest 2004; 34 (7): 513–514 Sir, Abdominal aortic aneurysm (AAA) is a chronic degen- erative disease occurring with a high incidence, up to 10%, in the over 65-year-old population [1]. The aneurysmal aortic wall is characterized by increased levels of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (UPA) [2–5], reflecting an activation of in- flammatory and resident cells, coupled with an imbalance with their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and plasminogen activator inhibitor (PAI-1) [6]. The resulting damage to the vessel wall and its progressive dilatation lead to an increased tensile stress to the wall that, in coupling with the destruction of elastic lamellae, may result in rupture. Although several studies have analyzed the wall of ruptured aneurysms, few data concerning the site of rupture are available [7]. In this context, six tissue samples were collected from one ruptured AAA, adjacent to the site of rupture and at increasing distance from the rupture. The steady-state mRNA level for matrix proteins, proteolytic enzymes involved in matrix degradation, and their inhibitors was measured by a quantitative RT-PCR procedure [8,9]. The expression of MMP-1, -2, -9, -12, -14 and uPA was 5–10-fold higher at the site of rupture than in the distant tissue samples (Fig. 1a) while MMP-3 and MMP-8, high at the site of rupture, were sporadically expressed at distance of it ( Fig. 1b). TIMP-1, -2, -3 and PAI- 1 were also largely expressed at the site of rupture (Fig. 1c). The elastin mRNA was not detected in the site of rupture but expressed, at varying levels, in the distant samples (Fig. 1d). The level of type I and III collagen mRNA was high at the site of rupture and declined outside of it (Fig. 1d). The MMP-1, -2, -9, -12, -14, uPA and the Correspondence to: N. Sakalihasan, Laboratory of Connective Tissues Biology and, Department of Cardiovascular Surgery, B35, CHU Sart-Tilman, University of Liège, 4000 Liège Belgium. Tel.: +32 4366 83 80; fax: +32 4366 71 64; e-mail: nsaka@chu.ulg.ac.be Received 30 April 2004; accepted 12 May 2004 Figure 1 (a–d) Steady-state level of mRNA for matrix metalloproteinases (a,b), their inhibitors (c) and fibrillar matrix proteins (d) in tissues sampled from the site of rupture ( R) and at increasing distance.The results are expressed in arbitrary units per unit of 28S ribosomal RNA. α1( I ), collagen type I; α1( III ), collagen type III.