doi: 10.1161/CIRCULATIONAHA.105.551572
(Circulation. 2006;113:438-445.)
© 2006 American Heart Association, Inc.
Vascular Medicine |
Matrix Metalloproteinase-8 and -9 Are Increased at the Site of Abdominal Aortic Aneurysm Rupture
From the Departments of Surgery (W.R.W.W., M.A., E.C.S., P.R.F.B.) and Pathology (J.L.J., P.N.F.), University of Leicester, Leicester, UK, and Department of Vascular Surgery (M.M.T.), St George’s Hospital Medical School, London, UK.
Reprint requests to Professor M.M. Thompson, Department of Vascular Surgery, 4th Floor, St. James Wing, St. Georges Hospital, NHS Trust, Blackshaw Rd, London, UK SW17 0QT. E-mail m.thompson{at}sghms.ac.uk
Received April 5, 2005; revision received October 22, 2005; accepted November 4, 2005.
Background— Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs).
Methods and Results— Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate.
Conclusions— A localized increase in MMP-8 and –9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.
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